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To investigate the different impact of optical coherence tomography (OCT)-derived vulnerable plaque features on future adverse events (AEs) according to the biological sex.The prospective multicenter CLIMA study (ClinicalTrials.gov: NCT02883088) enrolled 1003 patients with OCT plaque analysis of non-treated coronary plaques located in the proximal left anterior descending artery. Sex-specific differences in plaque composition and vulnerable features were described. We investigated the incidence of AEs, including cardiac death, any myocardial infarction and target vessel revascularization at 1-year.Among 1003 patients, 24.6% were women. Women were older and more frequently affected by chronic kidney disease. Dyslipidemia, prior MI and smoking habit were more common in men. At OCT analysis, women had shorter plaque length (p 0.001), ticker fibrous cap (p = 0.001), smaller maximum lipid arc (p = 0.019), lower macrophage infiltration (p 0.001) and intra-plaque layered tissue (p = 0.007). During follow-up, 65 AEs were registered. The presence of a thin fibrous cap and a large macrophage infiltration ( 67°) predicted AEs in both sexes. The presence of macrophages (HR 3.38, p = 0.018) and a small minimum lumen area (HR 4.97, p = 0.002) were associated with AEs in women but not in men, while a large lipid arc ( 180°) was associated with AEs in men (HR 2.56, p = 0.003) but not in women.This subanalysis of the CLIMA study investigated for the first-time sex-specific OCT features of plaque vulnerability associated with AEs. Local inflammation was associated with AEs in women and a large lipid arc was predictive in men. OCT may help develop sex-specific risk stratification strategies.

Background: In some randomized clinical trials, transradial access (TRA) compared with transfemoral access (TFA) was associated with lower mortality in patients with coronary artery disease undergoing invasive management. We analyzed the effects of TRA versus TFA across multicenter randomized clinical trials and whether these associations are modified by patient or procedural characteristics. Methods: We performed an individual patient data meta-analysis of multicenter randomized clinical trials comparing TRA with TFA among patients undergoing coronary angiography with or without percutaneous coronary intervention. The primary outcome was all-cause mortality and the co–primary outcome was major bleeding at 30 days. The primary analysis was conducted by 1-stage mixed-effects models on the basis of the intention-to-treat cohort. The effect of access site on mortality and major bleeding was assessed further by multivariable analysis. The relationship among access site, bleeding, and mortality was investigated by natural effect model mediation analysis with multivariable adjustment. Results: A total of 21 600 patients (10 775 TRA, 10 825 TFA) from 7 randomized clinical trials were included. The median age was 63.9 years, 31.9% were women, 95% presented with acute coronary syndrome, and 75.2% underwent percutaneous coronary intervention. All-cause mortality (1.6% versus 2.1%; hazard ratio, 0.77 [95% CI, 0.63–0.95]; P =0.012) and major bleeding (1.5% versus 2.7%; odds ratio, 0.55 [95% CI, 0.45–0.67]; P P interaction =0.003), indicating that the benefit of TRA was substantial in patients with moderate or severe anemia, whereas it was not significant in patients with milder or no baseline anemia. After adjustment, TRA remained associated with 24% and 51% relative risk reduction of all-cause mortality and major bleeding, respectively. A mediation analysis showed that the benefit of TRA on mortality was only partially driven by major bleeding prevention and ancillary mechanisms are required to fully explain the causal association. Conclusions: TRA is associated with lower all-cause mortality and major bleeding at 30 days compared with TFA. The effect on mortality was driven by patients with anemia. The reduction in major bleeding only partially explains the mortality benefit. Registration: URL: https://www.crd.york.ac.uk/prospero ; Unique identifier: CRD42018109664.

Intracoronary provocation testing with acetylcholine (ACh) is crucial for the diagnosis of functional coronary alterations in patients with suspected myocardial ischaemia and non-obstructive coronary arteries.Our intention was to assess the safety and predictive value for major adverse cardiovascular and cerebrovascular events (MACCE) in patients presenting with ischaemia with non-obstructive coronary arteries (INOCA) or with myocardial infarction with non-obstructive coronary arteries (MINOCA).We prospectively enrolled consecutive INOCA or MINOCA patients undergoing intracoronary ACh provocation testing.A total of 317 patients were enrolled: 174 (54.9%) with INOCA and 143 (45.1%) with MINOCA. Of these, 185 patients (58.4%) had a positive response to the ACh test. Complications during ACh provocative testing were all mild and transient and occurred in 29 (9.1%) patients, with no difference between patients with positive or negative responses to ACh testing, nor between INOCA and MINOCA patients. A history of paroxysmal atrial fibrillation, moderate/severe diastolic dysfunction and a higher QT dispersion at baseline electrocardiogram were independent predictors of complications. MACCE occurred in 30 patients (9.5%) during a median follow-up of 22 months. The incidence of MACCE was higher among patients with a positive ACh test (24 [13.0%] vs 6 [4.5%], p=0.017), and a positive ACh test was an independent predictor of MACCE.ACh provocation testing is associated with a low risk of mild and transient complications, with a similar prevalence in both INOCA and MINOCA patients. Importantly, ACh provocation testing can help to identify patients at higher risk of future clinical events, suggesting a net clinical benefit derived from its use in this clinical setting.

Aims The aim of this study was to assess the morphological characteristics and prognostic implications of the optical coherence tomography (OCT)-derived lipid core burden index (LCBI). Methods and results OCT-LCBI was assessed in 1003 patients with 1-year follow-up from the CLIMA multicentre registry using a validated software able to automatically obtain a maximum OCT-LCBI in 4 mm (maxOCT-LCBI4mm). Primary composite clinical endpoint included cardiac death, myocardial infarction, and target-vessel revascularization. A secondary analysis using clinical outcomes of CLIMA study was performed. Patients with a maxOCT-LCBI4mm ≥ 400 showed higher prevalence of fibrous cap thickness (FCT) 180° (OR 3.93, 95%CI 2.97–5.21; P < 0.001), minimum lumen area Conclusions A high maxOCT-LCBI4mm was related to poor outcome and vulnerable plaque features. This study represents a step further in the automated assessment of the coronary plaque risk profile.

The present investigation aims to study the interaction between systemic and intra-plaque inflammation in predicting cardiac events. We investigated C-reactive protein (CRP) levels as well as plaque inflammation with optical coherence tomography (OCT)-detected macrophages in the CLIMA study. 689 patients had admission CRP serum values reported, and high CRP values were defined as ≥ 2 mg/dl. The main study endpoint was a composite of cardiac death, myocardial infarction, and/or target vessel revascularization at 1-year follow-up. At multivariate Cox regression analysis, a large (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.2-4.3; p = 0.013) and superficial (HR 2.78, 95%CI 1.5-5.1; p = 0.001) macrophage arc was predicted of the main composite endpoint in patients with high CRP levels. Patients with large/superficial macrophage accumulation and low CRP levels were not at higher risk of adverse events. The presence of high CRP levels and large/superficial macrophage accumulation at OCT analysis identified patients at higher risk of clinical events.

Few data are available on the prevalence of right ventricle (RV) systolic dysfunction, assessed including RV strain, and RV to pulmonary artery (PA) coupling in patients with aortic stenosis (AS) submitted to TAVI and the early effect of the procedure. We performed standard and speckle tracking echocardiography in 80 patients with severe AS the day before TAVI and within 48 h after TAVI. In all patients we measured TAPSE/PASP (cut-off for RV-PA uncoupling 0.31) and in 60/80 we were able to analyze RV global longitudinal strain (RV-GLS) and RV free wall strain (RV-FWS). RVFAC and TAPSE were impaired in 8.3% while RV-GLS and RV-FWS in 45% and 33.3% respectively before TAVI. TAPSE/PASP 0.31 was documented in 7/80 patients (8.7%) before TAVI. These subjects differed from patients with TAPSE/PASP ≥ 0.31 for: enlarged left ventricular (LV) end-diastolic and end-systolic volumes (p 0.001), worst LV ejection fraction (p 0.001) and RVFAC (p 0.001), worst RV-GLS and RV-FWS (p = 0.01 and p = 0.03) and bigger right atrium (RA) area (p 0.001). After TAVI, RV systolic function did not improve while PASP significantly decreased (p = 0.005) driving the improvement of TAPSE/PASP (p = 0.01). Patients with TAPSE/PASP improvement (51%) differed from the others for worst pre-TAVI diastolic function (E/e' p = 0.045), RVFAC (p = 0.042), RV-GLS (p = 0.049) and RA area (p = 0.02). RV-GLS unveils RV systolic dysfunction in as much as 45% of patients with AS vs only 8.3% revealed by conventional echocardiography. RV systolic function does not significantly improve early after TAVI while RV-PA coupling does. Patients with lower TAPSE/PASP at baseline have worst LV and RV systolic function as well as larger RA. Patients who improve TAPSE/PASP after TAVI are those with worst diastolic function, RV systolic function and larger RA at baseline.

Background In the acute management of ST-elevation myocardial infarction (STEMI), glycoprotein IIb/IIIa inhibitors (GPIs) bolus not followed by intravenous infusion is potentially advantageous given their fast onset and offset of action, but clinical evidence in a contemporary setting is limited. Methods We collected data from consecutive STEMI patients admitted to the cardiac catheterization laboratory of the Fondazione Policlinico Universitario A. Gemelli from October 2017 to September 2019. Results Out of 423 consecutive STEMI patients, 297 met the inclusion and exclusion criteria and were included in the study. Of them, 107/297 (36%) received an intracoronary GPI bolus-only during primary percutaneous coronary intervention (PPCI) not followed by intravenous infusion and 190/297 (64%) received standard antithrombotic therapy. Of the 107 GPI-treated, 22/107 (21%) had P2Y12 inhibitor pre-treatment (adjunctive strategy) and 85/107 (79%) did not (bridging strategy). During hospital staying, there was no difference in the primary safety endpoint of TIMI major+minor bleeding (p=0.283), TIMI major (p=0.267) or TIMI minor (p=0.685) bleeding between groups. No stroke event occurred in the GPI group. Despite patients receiving GPI having a significantly higher intraprocedural ischemic burden, no significant differences were found in the efficacy outcomes between groups. Consistent findings were observed for patients receiving GPIs bolus before (bridging strategy) or after (adjunctive strategy) P2Y12 inhibitors, compared to those receiving standard therapy. Multivariate logistic regression analyses did not find any independent predictors significantly associated to the primary and secondary composite endpoints. Conclusions In a contemporary real-world population of STEMI patients undergoing PPCI, the use of intracoronary GPIs bolus-only in selected patients at high ischemic risk is safe and could represent a useful antithrombotic strategy both in those pre-treated and in those naive to P2Y12 inhibitors.

Aims Adenosine has been tested in several randomized controlled trials (RCTs) to minimize the incidence of coronary microvascular obstruction (CMVO). The aim of this study was to pool all the RCTs comparing intracoronary or intravenous adenosine versus placebo in patients with acute coronary syndrome (ACS) undergoing myocardial revascularization. Methods and results PubMed and Scopus electronic databases were scanned for eligible studies up to 5th June 2022. A total of 26 RCTs with 5843 patients were included. Efficacy endpoints were major adverse cardiac events (MACE), all-cause death, non-fatal myocardial infarction, and heart failure. Atrioventricular blocks and ventricular fibrillation/sustained ventricular tachycardia (VF/SVT) were the safety endpoints. Myocardial blush grade, thrombolysis in myocardial infarction (TIMI) flow grade, left ventricular ejection fraction (LVEF), infarct size, and ST-segment resolution were also assessed. Adenosine administration was not associated with any clinical benefit in terms of MACE, all-cause death, non-fatal myocardial infarction, and heart failure. However, adenosine was associated with an increased rate of advanced atrioventricular blocks and of VF/SVT in studies with total mean ischaemic time >3 h, compared to placebo. Remarkably, among patients undergoing percutaneous coronary intervention, adenosine was associated with reduced myocardial blush grade 0–1 and TIMI flow grade 0–2, compared to placebo. Furthermore, adenosine did not show favourable effects on LVEF and infarct size. Conclusion Adenosine infusion, as adjunctive therapy in ACS, was associated with an increased risk of advanced atrioventricular blocks and increased rates of adenosine-triggered ventricular arrhythmias in patients with long ischaemic time, without providing any clinical benefit compared to placebo.

BACKGROUND The radial artery is recommended by international guidelines as the default vascular access in patients with acute coronary syndromes (ACS) managed invasively. However, crossover from radial to femoral access is required in 4-10% of cases and has been associated with worse outcomes. No standardised algorithm exists to predict the risk of radial crossover. AIMS We sought to derive and externally validate a risk score to predict radial crossover in patients with ACS managed invasively. METHODS The derivation cohort consisted of 4,197 patients with ACS undergoing invasive management via the randomly allocated radial access from the MATRIX trial. Using logistic regression, we selected predictors of radial crossover and developed a numerical risk score. External validation was accomplished among 3,451 and 491 ACS patients managed invasively and randomised to radial access from the RIVAL and RIFLE-STEACS trials, respectively. RESULTS The MATRIX score (age, height, smoking, renal failure, prior coronary artery bypass grafting, ST-segment elevation myocardial infarction, Killip class, radial expertise) showed a c-index for radial crossover of 0.71 (95% CI: 0.67-0.75) in the derivation cohort. Discrimination ability was modest in the RIVAL (c-index: 0.64; 95% CI: 0.59-0.67) and RIFLE-STEACS (c-index: 0.66; 95% CI: 0.57-0.75) cohorts. A cut-off of ≥41 points was selected to identify patients at high risk of radial crossover. CONCLUSIONS The MATRIX score is a simple eight-item risk score which provides a standardised tool for the prediction of radial crossover among patients with ACS managed invasively. This tool can assist operators in anticipating and better addressing difficulties related to transradial procedures, potentially improving outcomes.

Background Percutaneous coronary intervention (PCI) is the milestone of treatment for patients with acute coronary syndrome (ACS). However, a considerable number of patients do not achieve a complete myocardial reperfusion since coronary microvascular obstruction (CMVO) might occur. Adenosine is one of the pharmacological strategies tested in several randomized controlled trials (RCTs) to minimize the incidence of CMVO. However, conflicting results have been reported so far. The aim of the present study was to evaluate all the RCTs comparing intracoronary or intravenous adenosine versus placebo as adjunctive therapy in patients with ACS undergoing PCI or thrombolysis. Methods PubMed and Scopus electronic databases were scanned for eligible studies up to June 5th, 2022. Our meta-analysis included 26 randomized RCTs with a total of 5843 patients involved. Primary endpoints were the rate of clinical events, defined as major adverse cardiovascular events (MACE), heart failure (HF), all-cause-death and non-fatal myocardial infarction (MI). The rate of advanced atrioventricular (AV) blocks and ventricular fibrillation/sustained ventricular tachycardia (VF/SVT) were considered as safety endpoints. Further subgroup analyses and meta regressions were conducted to evaluate the role of different procedural and non-procedural factors influencing the results. Finally, a secondary analysis was conducted only including RCTs enrolling patients with ST-segment elevation myocardial infarction (STEMI). Results Adenosine administration did not confer any significant clinical benefit in terms of reduction of MACE (RR 0.91 CI 0.79-1.05, p 0.16), all-cause-death (RR 0.90 CI0.74-1.09, p 0.28), non-fatal MI (RR 1 CI 0.74 - 1.35, p 0.44) and HF (RR 0.94 CI 0.77-1.16, p 0.59). Remarkably, adenosine was associated with a significant reduction of post-procedural CMVO parameters such as Myocardial Blush Grade (MBG) 0-1 (RR 0.69 CI 0.53-0.90, p 0.01) and Thrombolysis In Myocardial Infarction (TIMI) flow grade 0-2 (RR 0.67 CI 0.53-0.85, p 3 hours (RR 1.67 CI 1.14-2.42) Conclusions This is the most up-to-date meta-analysis summarizing the available evidence on adenosine safety and efficacy in the prevention or treatment of CMVO in ACS patients. Although adenosine improves surrogate parameters of myocardial perfusion, its use does not provide any clinical benefits. Additionally, adenosine infusion increases the risk of advanced AV blocks. Moreover, a longer ischemic time seems to be associated with a higher rate of adenosine-triggered ventricular arrhythmias, suggesting that higher myocardial ischemic damage may represent a substrate for adenosine arrhythmogenic effects.

Introduction Atherosclerotic plaque healing is a dynamic process that promotes plaque repair after destabilization. Previous studies showed that healed plaques are more common in patients with chronic coronary syndrome than in those with acute coronary syndrome, suggesting that they might be a marker of clinical stability. The mechanisms underlying plaque healing are not completely understood. The aim of the present study was to evaluate sex-based differences in plaque phenotype and healing of non-culprit coronary lesions by optical coherence tomography. Methods In this observational, single-center cohort study, we enrolled patients from the OCT Registry of the Fondazione Policlinico A Gemelli IRCCS. A total of 205 patients with both acute coronary syndromes or chronic coronary syndromes undergoing coronary angiography and intravascular OCT imaging of non-culprit vessels were included in the analysis and divided into two groups according to gender. Results Of 205 patients, 153 were male (75%) and 52 (25%) female. Compared with male patients, female patients had lower prevalence of lipid-rich plaque (40.4% vs. 57.7%; p=0.030), plaque rupture (7.7% vs. 21.2%; p=0.028) and cholesterol crystal (13.5% vs. 29.5%; p=0.022). Mean lipid arc and calcium depht were significantly lower in female patients than in male ones (118.0° ± 79.9° vs. 135.5° ± 77.9°; p=0.011; and 52.7 µm ± 79.2 µm vs. 72.3 µm ± 93.5 µm; p=0.007) while fibrous cap tended to be thicker (108.2 µm ± 70.4 µm vs. 96.2 µm ± 72.9 µm; p=0.055). Healed plaques were significantly more frequent in female patients than in male patients (51.9% vs 34.6%; p = 0.027). The prevalence of fibrous plaque, thrombi, neovascularization, diffuse calcifications and spotty calcification was not different between the two groups. Conclusion Females have a distinct atherosclerotic phenotype and healing capacity compared with male patients, including lower prevalence of lipid-rich plaque, cholesterol crystals and plaque ruptures and higher prevalence of healed plaques in non-culprit coronary lesions.

Background Several environmental and seasonal factors are thought to be crucial in the risk of acute coronary syndromes (ACS), including temperature, latitude, longitude, atmospheric air pressure, wind velocity and circadian period. However differences in coronary plaque composition according to season variation is still poorly understood. Purpose Our study aims to analyse the characteristics of non-culprit coronary plaques in patients undergoing optical coherence tomography evaluation (OCT) evaluation of the left anterior descending artery. Methods We included 1848 non-culprit coronary plaques from 1003 patients of the CLIMA registry. The season of OCT pullback acquisition was collected for each patient. Results Overall, median age was 66 years (56-74), with 24.6% of women and 53.4% of ACS. At patient-level analysis, patients admitted in summer were less frequently affected by hypertension (59.8% vs 69.4% in autumn, 68.5% in winter and 72% in spring; p=0.027) and chronic kidney disease (14.8% vs 15.9% in autumn, 10.3% in winter and 19.4% in spring; p=0.037) in. At lesion-level analysis, similar values of fibrous cap thickness, maximum lipid arc, length of plaques and presence of macrophages were observed (Table 1). Summer plaques had a smaller minimum lumen area than spring plaques (5.7±3.1 vs 5.1±239; p=0.044) and also a less frequent superficial macrophage infiltration (23% vs 36.1% in autumn, 30.5% in winter and 30.6% in spring; p=0.030) and presence of cholesterol crystals (16.7% vs 23.8% in autumn, 28.4% in winter and 22.1% in spring; p=0.037 than three other season). Table 1 Conclusions Coronary plaques during summer had less local sign of inflammation such superficial macrophage infiltration and cholesterol crystals. Further studies are needed to confirm these results and investigate clinical implications.

Introduction Pathological studies have shown that many atherosclerotic plaques destabilize without resulting in a clinical manifestation. Recent in vivo studies showed that healed plaques are more common in patients with chronic coronary syndrome (CCS) than in those with acute coronary syndrome (ACS), suggesting that they might be a marker of clinical stability. The aim of the present study was to evaluate the clinical impact of healed coronary plaques detected by optical coherence tomography (OCT) imaging. Methods A total of 208 patients with CCS or ACS who underwent OCT imaging of non-target/non-culprit vessels were enrolled. Only non-culprit segments were analyzed. Patients were divided into two groups according to the presence or absence of healed plaques detected by OCT. The incidence of major adverse cardiac events (MACE) at follow-up was assessed, defined as the composite of cardiac death, non-fatal myocardial infarction, and target vessel revascularization (TVR). Results Healed coronary plaques were observed in 39.7% of patients, and the prevalence was higher in those presenting with chronic coronary syndrome. Median follow-up time was 4 years, and was not different between the two groups. Patients with healed plaques had a significantly lower incidence of MACE at follow-up (13.6% vs 22%, p=0.019), mainly driven by a lower rate of non-fatal myocardial infarctions (4.9% vs 10.2%, p=0.05). The incidence of cardiac death and TVR was not significantly different between the two groups (1.2% vs. 3.1%, p=0.288; and 13.6% vs. 15.0%, p= 0.187, respectively). At multivariate Cox regression analysis, the presence of plaque disruption was an independent predictor of MACE (odds ratio [OR] 3.33, 95% confidence interval [CI] 1.39-7.98, p=0.007), while the presence of healed plaque was an independent protective factor (OR 0.44, 95% CI 0.22-0.89, p=0.022). Conclusions Healed coronary plaques detected by OCT imaging are associated with a favorable clinical outcome at long-term follow-up.

Aims The guide extension catheter (GEC) is a helpful tool to increase catheter support when facing complex percutaneous coronary intervention (PCI) in unfavorable coronary anatomies. The aim of this study was to describe indication, efficacy, and safety of the GEC in a high-volume center. Methods and results From 2014 to 2021, we retrospectively identified and analyzed 351 interventional cases in which GEC was used to complete the procedure. The endpoints of the study were PCI success, procedural success and device failure. GEC use increased over the years and was more frequently used by radial approach (92.1%) in elective setting (90.6%) and using the 6F size (95.3%). The GEC was mostly implemented as bail-out strategy (75.9%) with the aim to improve back-up (89.6%), less frequently to optimize catheter alignment or obtain selective coronary cannulation (10.4%). Intracoronary advancement was performed using the guidewire in 1.3% of cases, after positioning of a second “buddy” wire in 23.2%, with support of a deflated balloon at the distal tip in 12.2%, or with anchoring technique in 63.3%. Mean coronary deep intubation depth was 38.8±23.9mm. Vessel and lesion characteristics are reported in Table I. Overall, PCI success rate was 92.5%, while procedural success (PCI success without in hospital adverse event) was 88.6%. GEC was successfully used in 92.7% of patients with no device-dependent severe adverse events; in particular, failures were related to inability to cross the target lesion in 4.5% or to device–related complication in 2.85% of cases. Conclusions This large real-world registry on GEC use in complex PCI confirms the GEC as a valid and safe tool to increase backup support and overcome the limits of conventional technique during complex PCI.

Background: Multiple valvular heart disease is a very prevalent condition and represents a challenge in terms of diagnosis and treatment. In patients undergoing cardiac surgery, multiple valvular lesions are often treated during the same procedure. In older high-risk patients, the treatment of choice for VHD is usually percutaneous: transcatheter aortic valve replacement (TAVR) has been widely developed in the past years and percutaneous interventions on other valvular lesions are rapidly evolving. In patients undergoing TAVR, concomitant severe tricuspid regurgitation (TR) is frequent and it's a marker of advanced disease. After TAVR, secondary TR can regress to a lower grade; persistent TR is associated with higher incidence of heart failure and mortality, so an additional intervention for TR is reasonable. The aim of this case report is to highlight the role of staged percutaneous treatment of multiple VHD as a new paradigm, with reassessment of other valvular lesion severity after the first endovascular valvular treatment Case description: We describe a case of successful staged percutaneous treatment for severe low flow – low gradient aortic stenosis in a 71 years old patient, with previous mitral valve replacement with mechanical valve and tricuspid annuloplasty, atrial fibrillation and COPD (STS score 9.5%). Four years after cardiac surgery she experienced worsening dyspnea and two hospitalizations for pulmonary edema; the echocardiography showed significant biventricular dysfunction, severe aortic stenosis (low-flow low-gradient, with contractile reserve at dobutamine stress echocardiography) and normal function of mitral prosthesis. The case was evaluated by a multidisciplinary ‘’Heart Team’’ and a decision was made to undergo TAVR and then reassess TR severity and patient symptoms. She underwent TAVR (Evolut Pro 26 mm direct implantation) using a ‘’less-invasive totally-endovascular’’ technique, without complications. Two month later the echocardiogram showed a little improvement in left ventricular systolic function and persistent severe tricuspid regurgitations; the patient was still symptomatic for leg swelling and fatigue. After a second evaluation from the ‘’Heart Team’’, she underwent successful transcatheter tricuspid valve-in-ring implantation (Edwards Sapien3 29) via right transgiugular approach, with no complications. 19 months after she was alive, with no more hospitalization, NYHA class II, on heart failure therapy; at an echocardiogram tricuspid regurgitation was mild-to-moderate. Discussion: Multivalular heart disease patients more often have several comorbidities, greater cardiac damage, that leads to higher incidence of heart failure and death than single VHD. In particular right ventricular dysfunction and tricuspid regurgitation, mostly secondary to pressure overload, are associated with adverse outcomes in severe aortic stenosis, especially in the ‘’low flow- low gradient’’ group. After treatment of a severe valvular disease, hemodynamic changes in pression and volume loads may improve the function of other valves, so previous valvulopaties can regress to a lower stage of severity, with a better prognosis and the possibility to avoid a second valvular treatment and all the procedural risks. Conclusion There is lack of data in the literature concerning the management of multiple VDH, which does not allow for evidence-based recommendations in current guidelines. Transcatherer interventions offer the option of a staged approach and a tailored treatment, after accurate evaluation by the Heart Team.

Background It is unclear which diagnostic strategy for detecting coronary artery disease (CAD) yields better outcomes. We aimed to compare the clinical accuracy and efficacy of non-invasive and invasive diagnostic strategies for the initial assessment of patients with suspected stable CAD. Methods On March 16, 2022, we searched PubMed, Embase, and CENTRAL databases for randomised controlled trials comparing diagnostic strategies for CAD detection among patients with symptoms suggestive of stable CAD. Diagnostic modalities included coronary computed tomographic angiography (CCTA), cardiovascular magnetic resonance (CMR), exercise electrocardiography, invasive coronary angiography (ICA), single photon emission computed tomography-myocardial perfusion imaging (SPECT-MPI), and stress echocardiography. Functional tests were grouped into a single node for the primary analyses, while being analysed as separate nodes for the secondary analyses. Frequentist random-effect network meta-analyses were conducted to summarise the evidence. GRADE frameworks were applied to rate the certainty of findings. The primary efficacy outcome was trial-defined major adverse cardiovascular events (MACE) and the primary accuracy outcome was the rate of unnecessary angiography. The study was registered with PROSPERO (CRD42022329635). Results Twenty trials (n=27753 participants) were included. Compared with direct-ICA referral, CCTA and functional testing provided no significant difference in the risk of MACE (incidence rate ratios [IRRs] 0·87 [95% CI 0·65-1·17] and 1·19 [95% CI 0·87-1·62], respectively; moderate certainty) and a large reduction in the rate of unnecessary angiography (odds ratios 0·04 [95% CI 0·02-0·09] and 0·08 [95% CI 0·03-0·18], respectively; high certainty). Among non-invasive diagnostic strategies, CCTA significantly reduced the risk of MACE compared with functional testing (IRR 0·73, 95% CI 0·57-0·95; high certainty). The worse prognostic performance of functional testing was mainly driven by the poor efficacy of exercise electrocardiography (high certainty) and stress echocardiography (moderate to low certainty), whose risk of MACE was significantly reduced by CCTA (IRRs 0·56 [95% CI 0·42-0·75] and 0·59 [95% CI 0·42-0·81], respectively), SPECT-MPI (IRRs 0·56 [95% CI 0·41-0·77] and 0·59 [95% CI 0·43-0·81], respectively), and direct-ICA referral (IRRs 0·64 [95% CI 0·45-0·91] and 0·67 [95% CI 0·48-0·92], respectively), while non-significantly reduced by CMR (IRRs 0·71 [95% CI 0·47-1·06] and 0·74 [95% CI 0·53-1·04], respectively). Conclusion In patients with suspected stable CAD, an initial assessment with non-invasive diagnostic strategies is safe and addresses the low diagnostic yield of direct-ICA referral. CCTA is among the most effective strategies in terms of both clinical accuracy and efficacy. Among functional non-invasive tests, exercise electrocardiography and stress echocardiography may not be deemed effective diagnostic alternatives, while SPECT-MPI and CMR are valuable and feasible options, respectively.

The optimal access site for cardiac catheterization in patients with prior coronary artery bypass surgery (CABG) continues to be debated.We performed a random effects frequentist and Bayesian meta-analysis of 4 randomized trials and 18 observational studies, including 60,192 patients with prior CABG (27,236 in the radial group; 32,956 in the femoral group) that underwent cardiac catheterization. Outcomes included (1) access-site complications, (2) crossover to a different vascular access, (3) procedure time, and (4) contrast volume. Mean differences (MD) and 95% confidence interval (CI) were calculated for continuous outcomes and odds ratios (OR) and 95% CI for binary outcomes.Among randomized trials, crossover (OR: 7.63; 95% CI: 2.04, 28.51; p = 0.003) was higher in the radial group, while access site complications (OR: 0.96; 95% CI: 0.34, 2.87; p = 0.94) and contrast volume (MD: 15.08; 95% CI: -10.19, 40.35; p = 0.24) were similar. Among observational studies, crossover rates were higher (OR: 5.09; 95% CI: 2.43, 10.65; p 0.001), while access site complication rates (OR: 0.52; 95% CI: 0.30, 0.89; p = 0.02) and contrast volume (MD: -7.52; 95% CI: -13.14, -1.90 ml; p = 0.009) were lower in the radial group. Bayesian analysis suggested that the odds of a difference existing between radial and femoral are small for all endpoints except crossover to another access site.In a frequentist and Bayesian meta-analysis of patients with prior CABG undergoing coronary catheterization, radial access was associated with lower incidence of vascular access complications and lower contrast volume but also higher crossover rate.

Background and aims The use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for the treatment of cardiogenic shock (CS) may result in left ventricle overload and distension. Percutaneous microaxial flow pump Impella in addition to VA-ECMO (ECPELLA) is an emerging option to overcome these collateral effects. Aim of this study is to assess whether the addition of Impella to VA-ECMO is an effective and safe unloading strategy. Methods and results We performed a systematic literature review of studies comparing ECPELLA vs. ECMO alone in patients with CS. The primary endpoint was early mortality (in-hospital or 30-day mortality). The secondary endpoints were bleeding, need for kidney replacement therapy, haemolysis, infections, and limb ischaemia. A total of 3469 potentially relevant articles were screened and eight retrospective studies including 11.137 patients were selected. There was no significant difference in early mortality (Risk Ratio, RR 0.90, 95% CI 0.78–1.03) between ECPELLA and ECMO. Nevertheless, there was a borderline significant reduction in early mortality with ECPELLA (RR 0.74, 95% CI 0.55–1.00) at sensitivity analysis selectively including studies reporting propensity matched analysis. ECPELLA was associated with increased bleeding (RR 1.45, 95% CI 1.20–1.75), need for kidney replacement therapy (RR 1.54, 95% CI 1.19–1.99), haemolysis (RR 1.71, 95% CI 1.41–2.07) and limb ischaemia (RR 1.43, 95% CI 1.17–1.75) and with a non-significant increase in severe infections (RR 1.26, 95% CI 0.84–1.89), compared with ECMO alone. Conclusion Among patients with cardiogenic shock, ECPELLA is associated with increased complications compared with ECMO. Whether reducing ventricular overload with Impella among patients treated with ECMO reduces early mortality needs to be confirmed by further investigations.

Background: The mismatch between in-stent minimum lumen area (sMLA) and reference vessel lumen area, defined as stent underexpansion (SU), could be an important determinant of stent failure. We tested the clinical predictive value of absolute sMLA in comparison to relative SU in the context of the CLI-OPCI (Centro Per La Lotta Contro L’Infarto-Optimisation of Percutaneous Coronary Intervention) project registry. Methods: We retrospectively analyzed end procedural optical coherence tomography findings in 1211 patients (1422 lesions) undergoing percutaneous coronary intervention, assessing the prevalence and magnitude of residual SU and exploring correlation with outcome in comparison with sMLA. Results: In our series, both sMLA and SU were related to vessel size and anatomic lesion complexity. When compared with patients without adverse event at follow-up, those experiencing device-oriented cardiovascular events (composite of cardiac death, target vessel myocardial infarction, target lesion revascularization, and stent thrombosis) showed a lower sMLA (5.6±2.1 versus 6.1±2.1 mm 2 ; P =0.011) but a comparable degree of SU (11.6±14.1% versus 11.2±13.3%; P =0.734). The prespecified cutoff value of sMLA 2 , documented in 23.8% of cases, was confirmed as independent outcome predictor for device-oriented cardiovascular events (hazard ratio [HR], 2.05 [95% CI, 1.5–2.9]) including target lesion revascularization (HR, 2.43 [95% CI, 1.7–3.5]) and stent thrombosis (HR, 3.23 [95% CI, 1.7–6.3]). A residual SU of 10%, 20%, and 30% was observed in 38.0%, 18.2%, and 7.6% of cases, respectively. No grade of residual SU significantly increased the risk of stent failure, unless if an SU >20% was associated with an sMLA 2 (HR, 3.11 [95% CI, 1.7–5.6]). Finally, an association between stent overexpansion (ie, >110%) and device-oriented cardiovascular events was also observed (HR, 1.60 [95% CI, 1.1–2.3]). Conclusions: Final absolute sMLA and not relative SU was associated with an increased risk of stent failure. A variable grade of SU was common, but it resulted in being clinically relevant only when associated with an sMLA 2 .

Coronary artery obstruction (CAO) during transcatheter-aortic-valve replacement (TAVR) represents a main concern for TAVR safety in patients with low coronary take-off. To date, "snorkel" (also called chimney) technique, consisting of stent implantation from the coronary ostium to the aorta within the space between the valve frame and the aortic wall, is the most adopted strategy to prevent CAO. This technique is associated with the creation of complex valve/stent configuration that can hinder repeat coronary interventions. Due to this concern, we set up an original sequence for coronary protection aiming to ensure a more physiological TAVR frame/stent configuration. According to this technique, TAVR prosthesis is released with a "protection" system consisting of guiding catheter (GC), wire and stent inside the coronary artery with high CAO risk. In the case of CAO occurrence, the stent is released according to the snorkel technique. In the absence of complete CAO, a new GC is advanced inside the implanted TAVR prosthesis and the stent is deployed from the coronary artery up to the prosthesis. We herein report two cases of very high CAO risk where this technique was successfully used during last-generation self-expandable prostheses implantation (in a native aortic valve and in one prosthetic aortic valve). In conclusion, this "orthotopic snorkel-stenting in TAVR" (OST) technique represents a novel option for treating impeding CAO during TAVR. As compared with the "classic" snorkel technique, it allows avoiding stent implantation in some patients (who do not experience CAO) and may provide a more predictable and physiologic TAVR prosthesis/stent configuration in the case of stent implantation need.

BACKGROUND: On March 9, 2020, the Italian government imposed a national lockdown to tackle the COronaVIrus Disease 19 (COVID-19) pandemic, including stay at home recommendations. The precise impact of COVID-19 scare and lockdown on emergency access for acute myocardial infarction (MI) is still subject to debate. METHODS: Data on all patients undergoing invasive coronary angiography at 9 hospitals in the greater area of Rome, Italy, between February 19, 2020 and March 29, 2020, 9, 2020, were retrospectively collected. Incidence of ST-elevation MI (STEMI), and non-ST-elevation MI (NSTEMI), as well as corresponding percutaneous coronary intervention (PCI), was compared distinguishing two different 20-day time periods (before vs on or after March 10, 2020). RESULTS: During the study period, 1,068 patients underwent coronary angiography, 142 (13%) with STEMI and 169 (16%) with NSTEMI. The average daily number of STEMI decreased from 4.3 before the lockdown to 2.9 after the lockdown (p=0.021). Similarly, the average daily number of NSTEMI changed from 5.0 to 3.5 (p=0.028). The average daily number of primary PCI changed from 4.2 to 2.9 (p=0.030), while the average daily number of PCI for NSTEMI changed from 3.5 to 2.5 (p=0.087). For STEMI patients, the time from symptom onset to hospital arrival (onset-to-door time less than three hours) showed a significant increase after the lockdown (p=0.018), whereas door-to-balloon time did not change significantly from before to after the lockdown (p=0.609). CONCLUSIONS: The present study, originally reporting on the trends in STEMI and NSTEMI in the Rome area, highlights that significant decreases in the incidence of both acute coronary syndromes occurred between February 19, 2020 and March 29, 2020, together with increases in time from symptom onset to hospital arrival, luckily without changes in door-to-balloon time.

Valvular heart disease (VHD) requires optimized outpatient management that is generally considered to be best delivered by a dedicated, multidisciplinary team (Heart Valve Clinic, HVC). Although HVC is promoted by clinical guidelines and organized in many centers, real world outcome assessments are limited. Thus, we evaluated the performance, clinical and management outcomes during a 6-year experience with an original HVC model.By interrogating the local database, 1047 consecutive patients admitted to the HVC from January 2015 to October 2020 were found. Management and mortality were checked for all patients. After 3 years of HVC activity, in order to improve appropriateness and efficiency, access priority criteria were introduced. Thus, the study population was divided in two Period subgroups (before and after access criteria introduction) that were compared.A total of 1047 consecutive patients admitted to the HVC constituted the study population; 346 patients (33%) were recommended for invasive treatment. After a mean follow up of 25.7 ± 3.1 months, 37 patients (3.5%) died. When comparing study periods, statistically-significant increase inpatients' complexity and VHD severity was noticed in Period 2, also translating into higher rate of referral to intervention (39.0% vs. 29.4% in Period 1; p = 0.001). Finally, despite higher rate of elderly and frail patients, operative mortality was not jeopardized.The present study reports a comprehensive assessment of the characteristics and outcomes achieved through an original HVC model. Standardization of access criteria supports the HVC improvement.

Background Transaxillary route for structural and coronary percutaneous interventions represents a valid alternative access in patients with obstructive peripheral disease. Nevertheless, its widespread use is limited by a less manageable haemostasis procedure. Case summary In this case, we describe a minimalistic high-risk transcatheter aortic valve implantation (TAVI) procedure (TAVI Score 6.42%) conducted with a double arm approach (radial and axillary accesses) in an 88-year-old patient with severe aortic stenosis and multiple co-morbidities preventing both surgical (Society of Thoracic Surgeons mortality 7.9%) and percutaneous transfemoral approach (extensive peripheral artery disease). We also described the successful management of a complicated transaxillary haemostasis with this technique. Discussion In our cases, a minimalist double-arm approach was successfully used for TAVI procedure as an alternative to transfemoral approach assuring effective and safe management of vascular access haemostasis.

The differential outcomes across the age spectrum of transcatheter aortic valve implantation (TAVI) recipients are still debated. Aim of the study was to evaluate the clinical outcomes of oldest-old patients undergoing TAVI in the large "Registro Italiano GISE sull'impianto di Valvola Aortica Percutanea (RISPEVA)" registry. A total of 3,507 patients were stratified according to age: 1,381 were ≥85 years, 2,126 were85 years. Primary endpoints were death at 30-days and complete follow-up (FU) (medium 368 days). Cerebrovascular events, myocardial infarction, bleedings, vascular complications at 30-days and complete FU were considered. In the unadjusted analysis, 30-days mortality in the oldest-old group was higher than in younger patients (4.2% vs 2.4%; p = 0.007); this difference kept true also at complete FU (19.6% vs 15.9%; p = 0.014). After propensity score (PS) matching, the oldest-old population showed a higher mortality solely at 30-days (4.7% vs 2.4%; p = 0.016), while the survival at complete FU was similar to that of younger patients (20.1% vs 18.0%; p = 0.286). The incidence of non-fatal outcomes resulted comparable between the 2 groups, also after propensity score matching. At the multivariate logistic regression analysis procedural major or disabling bleedings, cerebrovascular events, cardiogenic shock resulted predictors of 30-days death in the oldest-old cohort. In conclusion, patients ≥85 years can safely undergo TAVI being not more exposed to procedural complications than those85 years; nevertheless they showed worse 30-days mortality, probably driven by reduced tolerance to complications. Passed the critical periprocedural phase, patients ≥85 years had a similar survival to those85 years with comparable risk profile.