Intentional coronary revascularization versus conservative therapy in patients after peripheral artery revascularization due to critical limb ischemia: the INCORPORATE trial.

OBJECTIVES: INCORPORATE trial was designed to evaluate whether default coronary-angiography (CA) and ischemia-targeted revascularization is superior compared to a conservative approach for patients with treated critical limb ischemia (CLI). Registered at clinicaltrials.gov (NCT03712644) on October 19, 2018. BACKGROUND: Severe peripheral artery disease is associated with increased cardiovascular risk and poor outcomes. METHODS: INCORPORATE was an open-label, prospective 1:1 randomized multicentric trial that recruited patients who had undergone successful CLI treatment. Patients were randomized to either a conservative or invasive approach regarding potential coronary artery disease (CAD). The conservative group received optimal medical therapy alone, while the invasive group had routine CA and fractional flow reserve-guided revascularization. The primary endpoint was myocardial infarction (MI) and 12-month mortality. RESULTS: Due to COVID-19 pandemic burdens, recruitment was halted prematurely. One hundred eighty-five patients were enrolled. Baseline cardiac symptoms were scarce with 92% being asymptomatic. Eighty-nine patients were randomized to the invasive approach of whom 73 underwent CA. Thirty-four percent had functional single-vessel disease, 26% had functional multi-vessel disease, and 90% achieved complete revascularization. Conservative and invasive groups had similar incidences of death and MI at 1 year (11% vs 10%; hazard ratio 1.21 [0.49-2.98]). Major adverse cardiac and cerebrovascular events (MACCE) trended for hazard in the Conservative group (20 vs 10%; hazard ratio 1.94 [0.90-4.19]). In the per-protocol analysis, the primary endpoint remained insignificantly different (11% vs 7%; hazard ratio 2.01 [0.72-5.57]), but the conservative approach had a higher MACCE risk (20% vs 7%; hazard ratio 2.88 [1.24-6.68]). CONCLUSION: This trial found no significant difference in the primary endpoint but observed a trend of higher MACCE in the conservative arm.

Quantitative flow ratio for the functional assessment of extracranial internal carotid artery stenosis.

BACKGROUND: In asymptomatic patients presenting with significant internal carotid artery (ICA) stenoses undergoing endovascular revascularization, a selective angiography before stenting (CAS) is required. Sometimes, angiographic findings could be discordant from non-invasive assessment and a tool able to evaluate functional relevance of the stenosis could be of value. We sought to evaluate the usefulness of quantitative flow ratio (QFR) as angiography-based tool for functional assessment of ICA stenoses. METHODS: We prospectively enrolled 50 asymptomatic patients undergoing CAS. Peak systolic velocity (PSV, cm/s) assessed at color Doppler echocardiography was used to identify significant stenoses (PSV >125 cm/s). At angiography, assessment of ICA stenosis was obtained visually (%DSVISUAL) and according NASCET criteria (%DSNASCET). Stenoses were considered significant if >60%. After exclusion of 20 vessels, QFR, area stenosis (AS, %) and minimal lumen area (MLA, mm2) were obtained in the remaining 80 vessels. RESULTS: At linear regression analysis, QFR significantly correlated with PSV (r2=0.52, P<0.001) as well as with %DSNASCET (r2=0.68, P<0.001) and %DSVISUAL (r2=0.71, P<0.001). Using PSV as reference, QFR showed good accuracy to predict functionally significant stenosis (AUC=0.98, P<0.001) with a cut-off value of 0.93. As compared with %DSNASCET and %DSVISUAL, QFR showed a significantly higher accuracy (61% vs. 73% vs. 94%, respectively; P<0.05), sensitivity (43% vs. 61% vs. 93%, respectively; P<0.05) and negative predictive value (46% vs. 51% vs. 85%, respectively; P<0.05) for detecting hemodynamically significant ICA stenoses. CONCLUSIONS: This study suggest the potential benefit of adopting QFR for functional assessment of extracranial ICA stenoses. These data should be validated in larger studies.

Cangrelor in contemporary patients with ST-segment elevation myocardial infarction pretreated with Ticagrelor: Pharmacodynamic data from the POMPEII study.

Background: There are limited data to assess pharmacodynamic (PD) profiles of patients with STEMI undergoing primary percutaneous coronary intervention (PCI) and receiving cangrelor after pretreatment with ticagrelor. Methods: The PharmacOdynaMic effects of cangrelor in PatiEnts wIth acute or chronIc coronary syndrome undergoing percutaneous coronary intervention (POMPEII) registry (NCT04790032) is a prospective study conducted at Federico II University of Naples enrolling all patients undergoing PCI receiving cangrelor at operator's discretion. PD assessments were performed with 3 assays: (1) the gold standard light transmittance aggregometry (LTA) (20- and 5-µM adenosine diphosphate [ADP] stimuli); (2) VerifyNow P2Y12-test; (3) Multiplate electrode aggregometry (MEA), ADP-test. Results: We analyzed 13 STEMI patients pretreated with ticagrelor within 1 h at the time they underwent primary PCI receiving cangrelor. All patients showed low maximal platelet aggregation at 30-minute during cangrelor infusion, as well as at 3 h and 4-6 h (corresponding to 1 h and 2-4 h after stopping cangrelor infusion) with no cases of high residual platelet reactivity. These results were consistent with all assays. Conclusions: PD data show that in contemporary real-world STEMI patients pretreated within 1 h with ticagrelor undergoing primary PCI, adding cangrelor resulted in fast and potent platelet inhibition, thus suggesting that cangrelor may bridge the gap until ticagrelor reaches its effect.

A comparison between radial artery compression devices for patent hemostasis after transradial percutaneous interventions.

OBJECTIVES: Patent hemostasis (PH) is essential for preventing radial artery occlusion (RAO) after trans-radial procedures; however, it remains unclear how it should be obtained. The aim of this multicenter randomized study was to evaluate whether the use of an adjustable device (AD), inflated with a pre-determined amount of air (AoA), was more effective than a non-adjustable device (non-AD) for achieving PH, thereby reducing the incidence of RAO. METHODS: We enrolled a total of 480 patients undergoing transradial procedure at 3 Italian institutions. Before the procedure, a modified Reverse Barbeau Test (mRBT) was performed in all patients to evaluate the AoA to be eventually inflated in the AD. After the procedure, patients were randomized into 2 groups: (1) AD Group, using TR-Band (Terumo) inflated with the pre-determined AoA; and 2) non-AD Group, using RadiStop (Abbott). An RBT was performed during compression to demonstrate the achievement of PH, as well as 24 hours later to evaluate the occurrence of RAO. RESULTS: PH was more often obtained in the AD Group compared with the non-AD Group (90% vs 64%, respectively, P less than .001), with no difference in terms of bleedings. RAO occurred more often in the non-AD Group compared with the AD Group (10% vs 3%, respectively, P less than .001). Of note, mRBT was effective at guiding AD inflation and identifying high-risk patients in whom PH was more difficult to obtain. CONCLUSIONS: The use of AD, filled with a predetermined AoA, allowed PH significantly more often compared with non-AD, providing a significantly reduced incidence of RAO.

"The INOCA-IT: Rationale and design of a multicenter registry investigating ischemia in patients with non-obstructive coronary artery (INOCA) disease in Italy".

BACKGROUND: Ischemia with non-obstructive coronary artery (INOCA) disease is being progressively acknowledged as one of the pathophysiological mechanisms of chronic coronary syndrome (CCS) in an increasingly wide range of clinical pictures. Although the research has already begun to move towards a defined diagnostic pathway and a specific medical therapy for this disease, at present it remains a clinical challenge, especially if not thoroughly investigated. METHODS AND RESULTS: The INOCA IT Multicenter Registry RF-2019-12369486 is a prospective, multicentric, non-randomized, single-arm, open label clinical study which aims to evaluate the efficacy of a stratified diagnostic and therapeutic approach on adverse events prevention and symptom relief in Italian patients with INOCA disease. The study population includes patients with a clinical presentation of CCS for angina and/or positive stress test for myocardial ischemia and evidence of non-obstructive coronary artery disease (CAD) at coronary angiography. In these patients a complete invasive coronary physiology assessment is performed with the guidewire-based measurement of coronary flow reserve (CFR) and index of microvascular resistance (IMR), followed by acetylcholine (ACh) spasm provocation test. On the basis of the results of coronary function testing, patients are stratified into different INOCA endotypes (coronary microvascular disease, vasospastic angina, microvascular spasm, non-cardiac chest pain) and given a tailored medical therapy in accordance with the latest scientific evidence. At one year follow-up the impact of such a target therapy on angina class and quality of life, as well as on cardiovascular adverse events (hospitalization and coronary revascularization) is evaluated. CONCLUSIONS: The INOCA-IT Multicenter Registry will inform clinicians on sex-specific prevalence of INOCA in Italy and will show the impact of a stratified diagnostic and therapeutic approach on symptoms burden and prognosis of INOCA patients.

Contemporary Evidence and Practice on Right Heart Catheterization in Patients with Acute or Chronic Heart Failure.

Heart failure (HF) has a global prevalence of 1-2%, and the incidence around the world is growing. The prevalence increases with age, from around 1% for those aged <55 years to >10% for those aged 70 years or over. Based on studies in hospitalized patients, about 50% of patients have heart failure with reduced ejection fraction (HFrEF), and 50% have heart failure with preserved ejection fraction (HFpEF). HF is associated with high morbidity and mortality, and HF-related hospitalizations are common, costly, and impact both quality of life and prognosis. More than 5-10% of patients deteriorate into advanced HF (AdHF) with worse outcomes, up to cardiogenic shock (CS) condition. Right heart catheterization (RHC) is essential to assess hemodynamics in the diagnosis and care of patients with HF. The aim of this article is to review the evidence on RHC in various clinical scenarios of patients with HF.

#FullPhysiology: a systematic step-by-step guide to implement intracoronary physiology in daily practice.

#FullPhysiology is a comprehensive and systematic approach to evaluate patients with suspected coronary disease using PressureWire technology (Abbott Vascular, Santa Clara, CA, USA). This advancement in technology enables the investigation of each component of the coronary circulation, including epicardial, microvascular, and vasomotor function, without significantly increasing procedural time or technical complexity. By identifying the predominant physiopathology responsible for myocardial ischemia, #FullPhysiology enhances precision medicine by providing accurate diagnosis and facilitating tailored interventional or medical treatments. This overview aims to provide insights into modern coronary physiology and describe a systematic approach to assess epicardial flow-limiting disease, longitudinal physiological vessel analysis, microvascular and vasomotor dysfunction, as well as post- percutaneous coronary intervention (PCI) physiological results.

[Ischemia with non-obstructive coronary artery disease: state-of-the-art review]. / L'ischemia miocardica in assenza di coronaropatia ostruttiva: stato dell'arte.

Chest pain affects more than 100 million people globally, however up to 70% of patients undergoing invasive angiography do not have obstructive coronary artery disease and ischemia with non-obstructive coronary artery disease (INOCA) is often a cause of the clinical picture. The symptoms reported by INOCA patients are very heterogeneous and often misdiagnosed as non-cardiac leading to under-diagnosis/investigation and under-treatment. The underlying pathophysiological mechanisms of INOCA are multiple and include coronary vasospasm and microvascular dysfunction. Most importantly, this condition must not be considered benign: compared to asymptomatic individuals, INOCA patients present an increased incidence of cardiovascular events, rehospitalizations, as well as impaired quality of life, with increasing costs for healthcare systems. The aims of this review are to describe the pathophysiological and clinical characteristics of INOCA and to provide guidance to the medical community on the diagnostic approaches and management of INOCA, also via a series of clinical case reports.

Uric acid plasma levels are associated with C-reactive protein concentrations and the extent of coronary artery lesions in patients with acute coronary syndromes.

Many studies have pointed out that inflammation plays a pivotal role in pathophysiology of acute coronary syndromes (ACS) because several inflammatory molecules impair the endothelial functions in the coronary circulation and promote atherothrombotic events. Recently, many clinical/experimental evidences indicate that elevated plasma levels of uric acid (UA) might be considered a risk factor for developing ACS. It has been reported that elevated UA doses impair physiologic functions of endothelial cells, shifting them toward a pro atherothrombotic phenotype. In the present manuscript, we investigated the relationship between UA plasma levels, inflammatory burden, and extension of coronary atherosclerotic disease in patients with ACS. Patients with a clinical presentation of ACS (ST-elevated and non-ST-elevated myocardial infarction) admitted to the Vanvitelli Catheterization Laboratory at Monaldi Hospital in 2019, before the COVID-19 pandemia, were retrospectively analyzed. Biochemical profile, type of ACS presentation, as well as extension of coronary atherosclerosis were assessed. A total of 132 ACS patients were included in the analysis, and grouped into 3 tertiles according to the UA values (UA < 4.72 mg/dl, UA between 4.72 and 6.15 mg/dl, and UA > 6.15 mg/dl). Patients with UA plasma levels ≥ 6.15 mg/dL showed higher levels of C-reactive protein (mean of 5.1 mg/dL) as compared to patients with lower UA plasma levels. Moreover, the former group of patients showed higher levels of cardiac troponin and CPK, and presented more often with multivessel disease and complex coronary stenosis (type C of Ellis classification). Even though monocentric and with limited sample size, the present study shows that plasma levels of UA and hs-CRP are elevated in ACS patients and are associated with a more severe coronary disease, suggesting a potential role of UA in the pathophysiology of acute coronary events.

Periprocedural myocardial infarction in patients undergoing complex versus noncomplex percutaneous coronary intervention.

BACKGROUND: Limited data are available on the risk of periprocedural myocardial infarction (MI) in patients undergoing complex versus noncomplex percutaneous coronary intervention (PCI). METHODS: We assessed the risk of periprocedural MI according to the fourth Universal definition of myocardial infarction (UDMI) and several other criteria among patients undergoing elective PCI in a prospective, single-center registry. Complex PCI included at least one of the following: 3 coronary vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, treatment of chronic total occlusion, and use of rotational atherectomy. RESULTS: Between 2017 and 2021, we included 1010 patients with chronic coronary syndrome, of whom 226 underwent complex PCI (22.4%). The rate of periprocedural MI according to the fourth UDMI was significantly higher in complex compared to noncomplex PCI patients (26.5% vs. 14.5%, p < 0.001). Additionally, periprocedural MI was higher in the complex PCI group using SCAI (4% vs. 1.1%, p = 0.009), ARC-2 (13.7% vs. 8.0%, p = 0.013), ISCHEMIA (5.8% vs. 1.7%, p = 0.002), and EXCEL criteria (4.9% vs. 2.0%, p = 0.032). SYNTAX periprocedural MI occurred at low rates in both groups (0.9% vs. 0.6%, p = 0.657). Complex PCI was an independent predictor of the fourth UDMI periprocedural MI (odds ratio [OR] 1.54, 95% confidence interval [CI]: 1.04-2.27, p = 0.031). CONCLUSIONS: In patients with chronic coronary syndrome undergoing elective PCI, complex PCI is associated with a significantly higher risk of periprocedural MI using multiple definitions. These findings highlight the importance of considering upfront this risk in the planning of complex PCI procedures.

Management of Non-Culprit Lesions in STEMI Patients with Multivessel Disease.

Multivessel disease is observed in approximately 50% of patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Data from randomized clinical trials has shown that complete revascularization in the STEMI setting improves clinical outcomes by reducing the risk of reinfarction and urgent revascularization. However, the timing and modality of revascularization of non-culprit lesions are still debated. PCI of non-culprit lesions can be performed during the index primary PCI or as a staged procedure and can be guided by angiography, functional assessment, or intracoronary imaging. In this review, we summarize the available evidence about the management of non-culprit lesions in STEMI patients with or without cardiogenic shock.

QFR-Based Virtual PCI or Conventional Angiography to Guide PCI: The AQVA Trial.

BACKGROUND: Post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) values ≥0.90 are associated with a low incidence of adverse events. OBJECTIVES: The AQVA (Angio-based Quantitative Flow Ratio Virtual PCI Versus Conventional Angio-guided PCI in the Achievement of an Optimal Post-PCI QFR) trial aims to test whether a QFR-based virtual percutaneous coronary intervention (PCI) is superior to a conventional angiography-based PCI at obtaining optimal post-PCI QFR results. METHODS: The AQVA trial is an investigator-initiated, randomized, controlled, parallel-group clinical trial. A total of 300 patients (356 study vessels) undergoing PCI were randomized 1:1 to receive either QFR-based virtual PCI or angiography-based PCI (standard of care). The primary outcome was the rate of study vessels with a suboptimal post-PCI QFR value, which was defined as <0.90. Secondary outcomes were procedure duration, stent length/lesion, and stent number/patient. RESULTS: Overall, 38 (10.7%) study vessels missed the prespecified optimal post-PCI QFR target. The primary outcome occurred significantly more frequently in the angiography-based group (n = 26, 15.1%) compared with the QFR-based virtual PCI group (n = 12 [6.6%]; absolute difference = 8.5%; relative difference = 57%; P = 0.009). The main cause of a suboptimal result in the angiography-based group is the underestimation of a diseased segment outside the stented one. There were no significant differences among secondary endpoints, although stent length/lesion and stent number/patient were numerically lower in the virtual PCI group (P = 0.06 and P = 0.08, respectively), whereas procedure length was higher in the virtual PCI group (P = 0.06). CONCLUSIONS: The AQVA trial demonstrated the superiority of QFR-based virtual PCI over angiography-based PCI with regard to post-PCI optimal physiological results. Future larger randomized clinical trials that demonstrate the superiority of this approach in terms of clinical outcomes are warranted. (Angio-based Quantitative Flow Ratio Virtual PCI Versus Conventional Angio-guided PCI in the Achievement of an Optimal Post-PCI QFR [AQVA]; NCT04664140).

Platelet Inhibition with Ticagrelor 60 mg Versus 90 mg Twice Daily in Elderly Patients with Acute Coronary Syndrome: Rationale and Design of the PLINY THE ELDER Trial.

BACKGROUND: Elderly status is steadily increasing among patients with acute coronary syndrome (ACS). Dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 receptor inhibitor is the cornerstone of treatment to prevent recurrent thrombotic complications in patients with ACS. However, DAPT in older patients is challenged by a concurrent heightened risk of ischemia and bleeding. The aim of this study is to evaluate the pharmacodynamic and pharmacokinetic profile of a lower dose of ticagrelor (60 mg twice daily) among elderly patients during the early phase of ACS. STUDY DESIGN: PLINY THE ELDER (PLatelet INhibition with two different doses of potent P2y12 inhibitors in THE ELDERly population) (NCT04739384) is a prospective, randomized, open-label, crossover trial to evaluate the non-inferiority of a lower dose of ticagrelor (60 mg twice daily) compared with a standard dose (90 mg twice daily) among elderly patients with ACS undergoing percutaneous coronary intervention (PCI). A total of 50 patients, aged 75 years or more, with indication to potent P2Y12 receptor inhibitors will be randomized within 3 days from PCI for the index ACS. Patients with indication to oral anticoagulant therapy, treatment with glycoprotein IIb/IIIa inhibitors, or active bleeding will be excluded. The primary endpoint is platelet reactivity determined by P2Y12 reaction units (PRU) (VerifyNow, Accumetrics, San Diego, CA, USA) after treatment with ticagrelor 60 or 90 mg twice daily for 14 days. Secondary endpoints will include other pharmacodynamic tests of ADP-induced aggregation (light transmittance aggregometry and multiple electrode aggregometry) and determination of pharmacokinetic profile (plasma levels of ticagrelor and its metabolite AR-C124910XX) by high performance liquid chromatography-tandem mass spectrometry. CONCLUSIONS: The PLINY THE ELDER trial will determine whether a lower dose of ticagrelor confers non-inferior platelet inhibition compared with the standard dose in the early phase of ACS among elderly patients undergoing PCI, informing future clinical investigation.

Impact of dual antiplatelet therapy duration on clinical outcome after coronary bifurcation stenting: results from the EuroBifurcation Club registry.

BACKGROUND: Optimal duration of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) of a bifurcation stenosis is still debated. We evaluated the impact of DAPT duration on clinical outcomes in all-comers patients undergoing bifurcation PCI included in the European Bifurcation Club (EBC) registry. METHODS: We enrolled 2284 consecutive patients who completed at least 18 months follow-up. The cumulative occurrence of major adverse cardiac and cardiovascular events (MACCE), defined as a composite of overall-death, non-fatal myocardial infarction (MI), target vessel revascularization (TVR) and stroke were evaluated. Bleedings classified as Bleeding Academic Research Consortium (BARC) ≥3 were evaluated too. RESULTS: Patients were divided into 3 groups: short DAPT (<6-months, N.=375); standard DAPT (≥6-months but ≤12-months, N.=636); prolonged DAPT (>12-months, N.=1273). At 24 months follow-up MACCE-free survival was significantly lower in short DAPT patients (Log-Rank: 45.23, P for trend <0.001). MACCE occurred less frequently in the prolonged DAPT group (148 [11.6%]) as compared with both the short (83 [22.1%] HR: 0.48 [0.37-0.63], P<0.001) and standard DAPT groups (137 [21.5%] HR:0.51 [0.41-0.65], P<0.001). These differences remain after propensity score adjustment (respectively, HR: 0.27 [0.20-0.36] and HR: 0.44 [0.34-0.57]). Such finding was consistent in patients presenting with both acute and chronic coronary syndromes. BARC≥3 bleedings were 0.3% in the standard DAPT, 1.6% in short and 1.9% in prolonged DAPT groups. CONCLUSIONS: In the "real-world" EBC registry of patients undergoing PCI of coronary artery bifurcation stenosis, a prolonged DAPT duration was associated with a significantly lower risk of MACCE and a potential increased risk of major bleedings.

Myocardial mass affects diagnostic performance of non-hyperemic pressure-derived indexes in the assessment of coronary stenosis.

Background Several non-hyperemic pressure-derived Indexes (NHPI) have been introduced for the assessment of coronary stenosis, showing a good correlation with fractional flow reserve (FFR). Notably, either the assessment of NHPI during adenosine administration (NHPIADO) or the Hybrid Approach (NHPIHA), combining NHPI with FFR, have been showed to increase the accuracy of such indexes. It remains unclear whether diagnostic performance might be affected by the extent of the subtended myocardial mass. METHODS: We enrolled consecutive patients with an intermediate coronary stenosis assessed with NHPI and FFR. NHPI were also measured during adenosine (ADO) administration (NHPIADO). The amount of jeopardized myocardium was assessed using the Duke Jeopardy Score (DJS). With FFR as reference, we assessed the accuracy of NHPI, NHPIADO and NHPIHA according to the extent of the subtended myocardium. RESULTS: One-hundred-seventy stenoses from 151 patients were grouped according to the DJS as follows: A) Small Extent (SE, n = 82); B) Moderate Extent (ME, n = 53); C) Large Extent (LE, n = 35). As compared with FFR, NHPI showed a significantly different accuracy, as assessed by the Youden's index, according to the extent of the jeopardized myocardium (SE: 0.39 ± 0.05, ME: 0.68 ± 0.06, LE: 0.28 ± 0.06, p < 0.001). Conversely, both the NHPIADO (SE: 0.76 ± 0.02, ME: 0.88 ± 0.02, LE: 0.82 ± 0.02, p = 0.72) and NHPIHA (SE: 0.82 ± 0.07, ME: 0.84 ± 0.02, LE: 0.88 ± 0.02, p = 0.70) allowed for a better diagnostic accuracy regardless of the amount of myocardium subtended. CONCLUSIONS: Diagnostic performance of NHPI might be affected by the extent of myocardial territory subtended by the coronary stenosis. A hybrid approach might be useful to overcome this limitation.

Invasive Assessment of Coronary Microcirculation: A State-of-the-Art Review.

A significant proportion of patients presenting with signs and symptoms of myocardial ischemia have no "significant" epicardial disease; thereby, the assessment of coronary microcirculation gained an important role in improving diagnosis and guiding therapy. In fact, coronary microvascular dysfunction (CMD) could be found in a large proportion of these patients, supporting both symptoms and signs of myocardial ischemia. However, CMD represents a diagnostic challenge for two main reasons: (1) the small dimension of the coronary microvasculature prevents direct angiographic visualization, and (2) despite the availability of specific diagnostic tools, they remain invasive and underused in the current clinical practice. For these reasons, CMD remains underdiagnosed, and most of the patients remain with no specific treatment and quality-of-life-limiting symptoms. Of note, recent evidence suggests that a "full physiology" approach for the assessment of the whole coronary vasculature may offer a significant benefit in terms of symptom improvement among patients presenting with ischemia and non-obstructive coronary artery disease. We analyze the pathophysiology of coronary microvascular dysfunction, providing the readers with a guide for the invasive assessment of coronary microcirculation, together with the available evidence supporting its use in clinical practice.

Impact of COVID-19 pandemic on timing and early clinical outcomes of transcatheter aortic valve implantation.

BACKGROUND: We sought to investigate the applicability and outcomes of a novel system to manage patients requiring transcatheter aortic valve implantation (TAVI) at a tertiary level hospital during the coronavirus disease-2019 (COVID-19) pandemic. METHODS: To analyse the impact of hospitalisation pathways during the pandemic on clinical outcomes of TAVI patients, the study population was divided into two groups (pre-pandemic and pandemic groups) and all perioperative/follow-up data were compared. The primary endpoint was all-cause mortality at 30 days; secondary endpoints included procedural success and short-term complications. RESULTS: A total of 315 patients received TAVI during the study period. Pandemic group (n = 77) showed a more complex baseline clinical profile (NYHA class III-IV, 70.1% vs. 56.3%; p = 0.03). The overall time to procedure was significantly longer during pandemic (56.9 ± 68.3 vs.37.7 ± 25.4; p = 0.004) while intensive care unit stay was shorter (2.2 ± 1.4 vs. 3.7 ± 3.9, p < 0.05). Hospitalisation length was similar in both groups as well as all-cause mortality rate and the incidence of major periprocedural complications. No case of infection by COVID-19 was reported among patients during the hospital stay. CONCLUSIONS: Comparative analysis of early clinical outcomes showed that COVID-19 pandemic did not affect the safety and effectiveness of TAVI as similar rates of procedural complications and all-cause mortality were reported than before February 2020. Despite the increased time lag between diagnosis and procedure and a more complex clinical profile of patients at baseline, the revised pathway of hospitalisation allowed to resume inpatient procedures while not affecting patients' and healthcare workers' safety.

Pathophysiology and mechanisms of Acute Coronary Syndromes: atherothrombosis, immune-inflammation, and beyond.

INTRODUCTION: The pathophysiology of atherosclerosis and its acute complications, such as the Acute Coronary Syndromes (ACS), is continuously under investigation. Immunity and inflammation seem to play a pivotal role in promoting formation and grow of atherosclerotic plaques. At the same time, plaque rupture followed by both platelets' activation and coagulation cascade induction lead to intracoronary thrombus formation. Although these phenomena might be considered responsible of about 90% of ACS, in up to 5-10% of acute syndromes, a non-obstructive coronary artery disease (MINOCA) might be documented. This paper gives an overview on atherothrombosis and immuno-inflammation processes involved in ACS pathophysiology, also emphasizing the pathological mechanisms potentially involved in MINOCA. AREAS COVERED: The relationship between immuno-inflammation and atherothrombosis is continuously updated by recent findings. At the same time, pathophysiology of MINOCA still remains a partially unexplored field, stimulating the research of potential links between these two aspects of ACS pathophysiology. EXPERT OPINION: Pathophysiology of ACS has been extensively investigated; however, several gray areas still remain. MINOCA represents one of these areas. At the same time, many aspects of immune-inflammation processes are still unknown. Thus, research should be continued to shed a brighter light on both these sides of "ACS" moon.

ADDED Index or Percentage Diameter of Residual Coronary Stenosis to Risk-Stratify Patients Presenting With STEMI.

BACKGROUND: We compared the prognostic value of the ADDED Index with visually estimated diameter (DS) of residual coronary stenosis (RS) in STEMI patients after successful PCI of the culprit lesion. Even though associated with a positive outcome, the functional assessment of non-culprit stenosis remains largely underused, especially in STEMI patients. The Angiography-DeriveD hEmoDynamic index (ADDED index) showed high accuracy to predict FFR and it might be used to better guide the diagnostic and therapeutic work-up of such patients. METHODS: We retrospectively included 596 patients grouped on the basis of either the ADDED Index (ADDED Negative (<2.23, n = 153) vs ADDED Positive (≥2.23, n = 129)) or the DS of the RS (RS Negative (<50%, n = 177) vs RS Positive (≥50%, n = 105)). Patients without any RS served as control (n = 314). Primary endpoints were: 1) major adverse cardiac events (MACE), composite of all-cause death, myocardial infarction (MI), clinically driven revascularizations (CDR); 2) non-culprit vessel oriented clinical events (VOCE), composite of all-cause death, non-culprit vessel related MI and CDR. RESULTS: At 24 months the rate of both MACE and VOCE was significantly higher in both the ADDED Positive and RS Positive groups. However, differently from patients in whom complete revascularization was deferred on the basis of the angiography (RS Negative), no additional risk was found for patients in the ADDED Negative group. CONCLUSIONS: In STEMI patients with MVD deferring treatment of RS on the basis of the ADDED index, rather than the visually estimated DS, is associated with a favorable clinical outcome.