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A metanalysis of available randomized controlled trials and observational studies comparing self-expanding (SE) and balloon-expandable (BE) bioprostheses in patients with small aortic annulus and aortic stenosis for short- and midterm hemodynamic and clinical outcomes was performed. A total of 21 studies with a total 8,647 patients (SE: n = 4,336 patients vs BE: n = 4,311 patients) were included. SE bioprostheses had a lower postoperative mean gradient at 30 days (Mean Difference [MD] -5.16, 95% confidence interval [CI] 4.7 to 5.5, p <0.001) and at 1 year (MD -6.6, 95%CI 6.1 to 7.03, p <0.001), with a larger indexed effective orifice area (0.17, 95% CI 0.13 to 0.22, p <0.001 and 0.17, 95% CI 0.08 to 0.27, p <0.001) at both time intervals. BE bioprostheses had a higher risk of 30-day and 1-year severe prosthesis-patient mismatch (risk ratio [RR] 1.07, 95% CI 1.04 to 1.09, p <0.001; RR 1.07, 95% CI 1.04 to 1.11, p <0.001). The 30-day and 1 year paravalvular leaks (RR 0.99, 95% CI 0.98 to 0.99, p <0.001; RR 0.89, 95% CI 0.82 to 0.95, p <0.001) and permanent pacemaker implantation (RR 0.97, 95% CI 0.94 to 0.99, p 0.01, I2 = 40%,) were lower in the BE group. BE bioprostheses were associated with a lower risk of in-hospital stroke (RR 0.99, 95% CI 0.98 to 1, p = 0.01). In conclusion, in patients with small aortic annulus and aortic stenosis, SE bioprostheses have superior hemodynamic performance but higher rates of paravalvular leak, permanent pacemaker implantation, and in-hospital stroke. BE bioprostheses were associated with a higher risk of severe prosthesis-patient mismatch., Competing Interests: Declaration of competing interest Dr. Thomas Pilgrim reports research, travel or educational grants to the institution without personal remuneration from Biotronik, Boston Scientific, Edwards Lifesciences, and ATSens; speaker fees and consultancy fees to the institution from Biotronik, Boston Scientific, Edwards Lifesciences, Abbott, Medtronic, Biosensors, and Highlife. Dr. Kay Woon Ho received speaker fees from Edwards Lifesciences, Medtronic, and Abbott Vascular. The remaining authors have no competing interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background : the role of the R202Q (c.605G>A, p.Arg202Gln) missense variant of the MEFV gene has been debated as either a benign polymorphism or a potentially pathogenic mutation. We report and discuss here the case of a young female with corticosteroid-dependent recurrent pericarditis carrying the homozygous R202Q variant, exhibiting distinctive clinical features possibly influenced by this genetic variant. Methods : a 30-year-old woman with a previous diagnosis of cancer and recent respiratory infection presented with severe pleuritic chest pain, hypotension, tachycardia, and fever. Initial diagnostic evaluation indicated cardiac tamponade, and emergent pericardiocentesis was performed. Despite initial treatment with NSAIDs, colchicine, and corticosteroids, the patient experienced multiple recurrences. Genetic testing identified homozygous R202Q variant in the MEFV gene. Given the corticosteroid dependency and recurrent nature of her condition, IL-1 inhibitor anakinra was introduced, leading to significant improvement, although tapering below 150 mg per week failed to prevent recurrences. Results : the introduction of anakinra resulted in rapid symptom relief and resolution of pericardial effusion. However, attempts to taper or discontinue anakinra led to pericarditis recurrences. Ultimately, a maintenance dose of 50 mg every three days was established, which maintained remission for 18 months without recurrence. Despite multiple tapering attempts, further reduction in anakinra dosage was unsuccessful without triggering relapses. Conclusions : the R202Q variant, although typically considered benign, may contribute to an autoinflammatory phenotype resembling familial Mediterranean fever. This case underscores the potential pathogenicity of the homozygous R202Q variant in recurrent pericarditis and its responsiveness to IL-1 inhibition. In patients with corticosteroid-dependent recurrent pericarditis, genetic testing for the R202Q variant should be considered when anti-IL-1 drugs cannot be withdrawn. Further studies are warranted to elucidate the variant's role in pericardial inflammation and guide personalized treatment strategies.

Background: Despite evidence supporting use of fractional flow reserve (FFR) and instantaneous waves-free ratio (iFR) to improve outcome of patients undergoing coronary angiography (CA) and percutaneous coronary intervention, such techniques are still underused in clinical practice due to economic and logistic issues., Objectives: We aimed to develop an artificial intelligence (AI)-based application to compute FFR and iFR from plain CA., Methods and Results: Consecutive patients performing FFR or iFR or both were enrolled. A specific multi-task deep network exploiting 2 projections of the coronary of interest from standard CA was appraised. Accuracy of prediction of FFR/iFR of the AI model was the primary endpoint, along with sensitivity and specificity. Prediction was tested both for continuous values and for dichotomous classification (positive/negative) for FFR or iFR. Subgroup analyses were performed for FFR and iFR.A total of 389 patients from 5 centers were enrolled. Mean age was 67.9 ± 9.6 and 39.2% of patients were admitted for acute coronary syndrome. Overall, the accuracy was 87.3% (81.2-93.4%), with a sensitivity of 82.4% (71.9-96.4%) and a specificity of 92.2% (90.4-93.9%). For FFR, accuracy was 84.8% (77.8-91.8%), with a sensitivity of 81.9% (69.4-94.4%) and a specificity of 87.7% (85.5-89.9%), while for iFR accuracy was 90.2% (86.0-94.6%), with a sensitivity of 87.2% (76.6-97.8%) and a specificity of 93.2% (91.7-94.7%, all confidence intervals 95%)., Conclusion: The presented machine-learning based tool showed high accuracy in prediction of wire-based FFR and iFR., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Stroke after durable left ventricular assist device (d-LVAD) implantation portends high mortality. The incidence of ischemic and hemorrhagic stroke and the impact on stroke outcomes of temporary mechanical circulatory support (tMCS) management among patients requiring bridge to d-LVAD with micro-axial flow-pump (mAFP, Abiomed) is unsettled., Methods: Consecutive patients, who underwent d-LVAD implantation after being bridged with mAFP at 19 institutions, were retrospectively included. The incidence of early ischemic and hemorrhagic stroke after d-LVAD implantation (<60 days) and association of pre-d-LVAD characteristics and peri-procedural management with a specific focus on tMCS strategies were studied., Results: Among 341 patients, who underwent d-LVAD implantation after mAFP implantation (male gender 83.6%, age 58 [48-65] years, mAFP 5.0/5.5 72.4%), the early ischemic stroke incidence was 10.8% and early hemorrhagic stroke 2.9%. The tMCS characteristics (type of mAFP device and access, support duration, upgrade from intra-aortic balloon pump, ECMELLA, ECMELLA at d-LVAD implantation, hemolysis, and bleeding) were not associated with ischemic stroke after d-LVAD implant. Conversely, the device model (mAFP 2.5/CP vs. mAFP 5.0/5.5: HR 5.6, 95%CI 1.4-22.7, p = 0.015), hemolysis on mAFP support (HR 10.5, 95% CI 1.3-85.3, p = 0.028) and ECMELLA at d-LVAD implantation (HR 5.0, 95% CI 1.4-18.7, p = 0.016) were associated with increased risk of hemorrhagic stroke after d-LVAD implantation. Both early ischemic (HR 2.7, 95% CI 1.9-4.5, p < 0.001) and hemorrhagic (HR 3.43, 95% CI 1.49-7.88, p = 0.004) stroke were associated with increased 1-year mortality., Conclusions: Among patients undergoing d-LVAD implantation following mAFP support, tMCS characteristics do not impact ischemic stroke occurrence, while several factors are associated with hemorrhagic stroke suggesting a proactive treatment target to reduce this complication., (© 2024 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Introduction: Spontaneous coronary artery dissection (SCAD) is a rare cause of acute myocardial infarction (AMI), which primarily affects young women without traditional cardiovascular risk factors, often presenting as sudden cardiac death. This study aims to investigate the prevalence, characteristics, predictors, and outcomes of cardiac arrest in SCAD patients., Methods: The DISCO IT/SPA registry, an international retrospective multicenter study, enrolled 375 SCAD patients from 26 centers in Italy and Spain. Patients were categorized based on the presence or absence of cardiac arrest at admission. Data on demographics, clinical presentation, treatment, angiographic findings, and outcomes were collected. Angiograms were independently reviewed, and outcomes included major adverse cardiovascular events (MACE) and in-hospital bleeding., Results: Among 375 SCAD patients, 20 (5.3%) presented with cardiac arrest. Both groups were similar in age, gender distribution, and conventional risk factors, except for a lower prevalence of dyslipidemia in the cardiac arrest group. ST-segment elevation myocardial infarction (STEMI) presentation and angiographic type 2b were independent predictors of cardiac arrest. Revascularization was more frequent in the cardiac arrest group. In-hospital outcomes, except for longer hospitalization, did not differ. On follow-up (average 21 months), MACE rates were similar between groups., Conclusions: Cardiac arrest is a notable complication in SCAD, mostly presenting with ventricular fibrillation. The prognosis of SCAD patients presenting with cardiac arrest did not differ from those without, reporting a similar rate of events both in-hospital and during long-term follow-up. STEMI presentation and angiographic type 2b were identified as independent predictors of cardiac arrest in SCAD., (Copyright © 2023. Published by Elsevier B.V.)

Aims: Haemodynamic assessment can be determinant in phenotyping cardiogenic shock (CS) and guiding patient management. Aim of this study was to evaluate the correlation between echocardiographic and invasive assessment of haemodynamics in acute decompensated heart failure-related CS (ADHF-CS)., Methods and Results: All consecutive ADHF-CS patients (SCAI shock stage ≥B) undergoing right heart catheterization (RHC) between 2020 and 2022 were prospectively enrolled. Patients underwent echocardiography 30 min before RHC. The evaluated haemodynamic parameters and their echocardiographic estimates ('e') comprised cardiac index (CI), wedge pressure (WP), pulmonary artery pressures (PAP), cardiac power output (CPO) and pulmonary artery pulsatility index (PAPi). Hundred and one ADHF-CS patients (56 ± 11 years, 64% SCAI shock stage C, left ventricular ejection fraction 29 ± 5%) were included. Good correlation was found for CI, systolic PAP, RAP, and CPO (Pearson r > 0.8 for all), moderate correlation for ePAPi (r = 0.67) and PVR (r = 0.51), while estimation of WP was weak. The sensitivity and specificity of eCI to identify low output state (CI ≤2.2 L/min/m2) were 0.97 and 0.73, respectively, those of eWP for elevated filling pressures (WP >15 mmHg) were 0.84 and 0.55, those of ePAPs for PAPs ≥35 mmHg were 0.87 and 0.63, those of eCPO for CPO <0.6 W were 0.76 and 0.85, those of ePAPi for PAPi <1.85 were 0.89 and 0.92. Echocardiographic phenotyping of CS showed a good agreement with invasive classification (K value 0.457, P < 0.001)., Conclusion: Echocardiographic estimation of haemodynamics and subsequent phenotypization of CS is feasible with good agreement with invasive evaluation., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Spontaneous coronary artery dissection (SCAD) is a rare but significant cause of acute coronary syndrome (ACS), primarily affecting young women, often during pregnancy. Despite its rarity, SCAD poses challenges due to limited evidence on management strategies. This review examines the current state of art of SCAD management, integrating interventional and clinical insights from recent studies. The epidemiology of SCAD is related to its elusive nature, representing only a small fraction of ACS cases, while certainly underestimated. Proposed risk factors include genetic, hormonal, and environmental influences. Angiographic classification may help in SCAD diagnosis, but confirmation often relies on intracoronary imaging. Conservative management constitutes the primary approach, showing efficacy in most cases, although optimal antiplatelet therapy (APT) remains debated due to bleeding risks associated with intramural hematoma. Revascularization is reserved for high-risk cases, guided by angiographic and clinical criteria, with a focus on restoring flow rather than resolving dissection. Interventional strategies emphasize a minimalist approach to reduce complications, utilizing techniques such as balloon dilation and stent placement tailored to individual cases. Long-term outcomes highlight the risk of recurrence, necessitating vigilant follow-up and arrhythmic risk assessment, particularly in patients presenting with ventricular arrhythmias. In conclusion, SCAD management always represents a challenge for the physician, both from a clinical and interventional point of view. Recent clinical evidence and a multidisciplinary approach are vital for optimizing patient outcomes and preventing recurrence. This review offers a concise framework for navigating the complexities of SCAD management in clinical practice and proposes an algorithm for its management., Competing Interests: The authors declare no conflict of interest. Fabrizio D’Ascenzo is serving as one of the Editorial Board members of this journal. We declare that Fabrizio D’Ascenzo had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Dimitris Tousoulis., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Background: Electrical Storm (ES) is a life-threatening condition requiring a rapid management. Percutaneous Stellate Ganglion Block (PSGB) proved to be safe and effective on top of standard therapy, but no data are available about its early use., Methods: We considered all patients enrolled from 1st July 2017 to 30th April 2024 in the STAR registry (STellate ganglion block for Arrhythmic stoRm), a multicentre, international, observational, prospective registry. We aimed to assess the effectiveness of the first PSGB only. Patients were divided into two groups depending on whether they received PSGB before (Early-PSGB, often due to AAD contraindication) or after (Delayed-PSGB) intravenous antiarrhythmic drugs (AADs other than beta-blockers)., Results: We considered 180 PSGB (26 Early-PSGB and 154 AAD-first). In the early-PSGB group we observed a statistically significant reduction of treated arrhythmic events in the hour after PSGB compared to the hour before: 0 (0-0) vs 4.5 (1-10), p<0.001 and the extent of the reduction was similar in the Early-PSGB and delayed-PSGB group [-4.5 (-7 to -2) vs. -2.5 (-3.5 to -1.5), p=ns]. The percentage of patients free from arrhythmias was similar in the two groups up to 12 hours after PSGB (81%vs 84%, p=0.6 after one hour; 77% vs 79%, p=0.8 at three hours and 65% vs 69%, p= 0.7 after 12 hours)., Conclusions: PSGB proved to be effective also when used early in the treatment of ES. Due to its rapidity of action, our results may suggest its early use to reduce the number of defibrillations and possibly to reduce the likelihood of a refractory ES., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The identification of acute cardioprotective strategies against myocardial ischemia/reperfusion (I/R) injury that can be applied in the catheterization room is currently an unmet clinical need and several interventions evaluated in the past at the pre-clinical level have failed in translation. Autonomic imbalance, sustained by an abnormal afferent signalling, is a key component of I/R injury. Accordingly, there is a strong rationale for neuromodulation strategies, aimed at reducing sympathetic activity and/or increasing vagal tone, in this setting. In this review we focus on cervical vagal nerve stimulation (cVNS) and on transcutaneous auricular vagus nerve stimulation (taVNS); the latest has the potential to overcome several of the issues of invasive cVNS, including the possibility of being used in an acute setting, while retaining its beneficial effects. First, we discuss the pathophysiology of I/R injury, that is mostly a consequence of the overproduction of reactive oxygen species. Second, we describe the functional anatomy of the parasympathetic branch of the autonomic nervous system and the most relevant principles of bioelectronic medicine applied to electrical vagal modulation, with a particular focus on taVNS. Then, we provide a detailed and comprehensive summary of the most relevant pre-clinical studies of invasive and non-invasive VNS that support its strong cardioprotective effect whenever there is an acute or chronic cardiac injury and specifically in the setting of myocardial I/R injury. The potential benefit in the emerging field of post cardiac arrest syndrome (PCAS) is also mentioned. Indeed, electrical cVNS has a strong anti-adrenergic, anti-inflammatory, antioxidants, anti-apoptotic and pro-angiogenic effect; most of the involved molecular pathways were already directly confirmed to take place at the cardiac level for taVNS. Pre-clinical data clearly show that the sooner VNS is applied, the better the outcome, with the possibility of a marked infarct size reduction and almost complete left ventricular reverse remodelling when VNS is applied immediately before and during reperfusion. Finally, we describe in detail the limited but very promising clinical experience of taVNS in I/R injury available so far., (© 2024. The Author(s).)

Background and Objective: Atrial fibrillation (AF) is the most common cardiac arrhythmia, inducing accelerated and irregular beating. Beside well-known disabling symptoms - such as palpitations, reduced exercise tolerance, and chest discomfort - there is growing evidence that an alteration of deep cerebral hemodynamics due to AF increases the risk of vascular dementia and cognitive impairment, even in the absence of clinical strokes. The alteration of deep cerebral circulation in AF represents one of the least investigated among the possible mechanisms. Lenticulostriate arteries (LSAs) are small perforating arteries mainly departing from the middle cerebral artery (MCA) and susceptible to small vessel disease, which is one of the mechanisms of subcortical vascular dementia development. The purpose of this study is to investigate the impact of different LSAs morphologies on the cerebral hemodynamics during AF., Methods: By combining a computational fluid dynamics (CFD) analysis of LSAs with 7T high-resolution magnetic resonance imaging (MRI), we performed different CFD-based multivariate regression analyses to detect which geometrical and morphological vessel features mostly affect AF hemodynamics in terms of wall shear stress. We exploited 17 cerebral 7T-MRI derived LSA vascular geometries extracted from 10 subjects and internal carotid artery data from validated 0D cardiovascular-cerebral modeling as inflow conditions., Results: Our results revealed that few geometrical variables - namely the size of the MCA and the bifurcation angles between MCA and LSA - are able to satisfactorily predict the AF impact. In particular, the present study indicates that LSA morphologies exhibiting markedly obtuse LSA-MCA inlet angles and small MCA size downstream of the LSA-MCA bifurcation may be more prone to vascular damage induced by AF., Conclusions: The present MRI-based computational study has been able for the first time to: (i) investigate the net impact of LSAs vascular morphologies on cerebral hemodynamics during AF events; (ii) detect which combination of morphological features worsens the hemodynamic response in the presence of AF. Awaiting necessary clinical confirmation, our analysis suggests that the local hemodynamics of LSAs is affected by their geometrical features and some LSA morphologies undergo greater hemodynamic alterations in the presence of AF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: The impact of prosthesis-patient mismatch (PPM) on major endpoints after transcatheter aortic valve replacement (TAVR) is controversial and the effects on progression of heart damage are poorly investigated. Therefore, our study aims to evaluate the prevalence and predictors of PPM in a "real world" cohort of patients at intermediate and low surgical risk, its impact on mortality and the clinical-echocardiographic progression of heart damage., Methods: 963 patients who underwent TAVR procedure between 2017 and 2021, from the RECOVERY-TAVR international multicenter observational registry, were included in this analysis. Multiparametric echocardiographic data of these patients were analyzed at 1-year follow-up (FU). Clinical and echocardiographic features were stratified by presence of PPM and PPM severity, as per the most current international recommendations, using VARC-3 criteria., Results: 18% of patients developed post-TAVR. PPM, and 7.7% of the whole cohort had severe PPM. At baseline, 50.3% of patients with PPM were male (vs 46.2% in the cohort without PPM, P = .33), aged 82 (IQR 79-85y) years vs 82 (IQR 78-86 P = .46), and 55.6% had Balloon-Expandable valves implanted (vs 46.8% of patients without PPM, P = .04); they had smaller left ventricular outflow tract (LVOT) diameter (20 mm, IQR 19-21 vs 20 mm, IQR 20-22, P = .02), reduced SVi (34.2 vs 38 mL/m 2 , P < .01) and transaortic flow rate (190.6 vs 211 mL/s, P < .01). At predischarge FU patients with PPM had more paravalvular aortic regurgitation (moderate-severe AR 15.8% vs 9.2%, P < .01). At 1-year FU, maladaptive alterations of left ventricular parameters were found in patients with PPM, with a significant increase in end-systolic diameter (33 mm vs 28 mm, P = .03) and a significant increase in left ventricle end systolic indexed volume in those with moderate and severe PPM (52 IQR 42-64 and 52, IQR 41-64 vs 44 IQR 35-59 in those without, P = .02)). No evidence of a significant impact of PPM on overall (P = .71) and CV (P = .70) mortality was observed. Patients with moderate/severe PPM had worse NYHA functional class at 1 year (NYHA III-IV 13% vs 7.8%, P = .03). Prosthesis size≤23 mm (OR 11.6, 1.68-80.1) was an independent predictor of PPM, while SVi (OR 0.87, 0.83-0.91, P < .001) and LVOT diameter (OR 0.79, 0.65-0.95, P = .01) had protective effect., Conclusions: PPM was observed in 18% of patients undergoing TAVR. Echocardiographic evaluations demonstrated a PPM-related pattern of early ventricular maladaptive alterations, possibly precursor to a reduction in cardiac function, associated with a significant deterioration in NYHA class at 1 year. These findings emphasize the importance of prevention of PPM of any grade in patients undergoing TAVR procedure, especially in populations at risk., Competing Interests: Declaration of competing interest The authors have no conflict of interest to report related to this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Beta-blockers are a crucial part of post-myocardial infarction (MI) pharmacological therapy. Recent studies have raised questions about their efficacy in patients without reduced left ventricular ejection fraction (LVEF). This study aims to assess adherence to beta-blockers after discharge for ST-segment elevation myocardial infarction (STEMI) and the impact of adherence on outcomes based on LVEF at discharge. The retrospective registry FAST-STEMI evaluated real-world adherence to main cardiovascular drugs in STEMI patients between 2012 and 2017 by comparing purchased tablets to expected ones at one year through pharmacy registries. Optimal adherence was defined ≥80%. Primary outcomes included all-cause and cardiovascular death, while secondary outcomes were myocardial infarction, major/minor bleeding events, and ischemic stroke The study included 4688 patients discharged on beta-blockers. Mean age was 64 ± 12.3 years, 76% were male, and mean LVEF was 49.2 ± 8.8%. Mean adherence at one year was 87.1%. Optimal adherence was associated with lower all-cause (adjHR 0.62, 95%CI 0.41-0.92, p 0.02) and cardiovascular mortality (adjHR 0.55, 95%CI 0.26-0.98, p 0.043). In LVEF ≤40% patients, optimal adherence was linked to reduced all-cause and cardiovascular mortality but this was not found either in patients with preserved or mildly reduced LVEF. Predictors of cardiovascular mortality included older age, chronic kidney disease, male gender, and atrial fibrillation. Optimal adherence to beta-blocker therapy in all-comers STEMI patients reduced all-cause and cardiovascular mortality at 1 year; once stratified by LVEF, this effect is confirmed only in patients with reduced LVEF (< 40%) at hospital discharge., Competing Interests: Conflicts of interest: none, (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Data on glycoprotein IIb/IIIa inhibitor (GPI) use in real-world acute coronary syndrome (ACS) patients following the introduction of potent P2Y12 inhibitors and newer-generation stents are scant. Here, we aimed to assess the utilization, effectiveness, and safety of GPI in a large prospective multicentre cohort of contemporary ACS patients., Methods and Results: SPUM-ACS prospectively recruited patients presenting with ACS between 2009 and 2017. The primary endpoint of the present study was major adverse cardiovascular events (MACE), a composite of all-cause death, non-fatal myocardial infarction, and non-fatal stroke at 1 year. Secondary endpoints were defined as any bleeding events, Bleeding Academic Research Consortium (BARC) 3-5 bleeding, and net adverse cardiovascular events (NACE). A total of 4395 ACS patients were included in the analysis. GPI-treated patients had more total coronary artery occlusion (56% vs. 35%, P < 0.001) and thrombus (60% vs. 35%, P < 0.001) at angiography. Among the propensity score-matched (PSM) population (1992 patients equally split into two groups), GPI-treated patients showed lower risk of MACE [PSM adjusted hazard ratio (HR) 0.70, 95% CI 0.49-0.99], but a higher risk of any (PSM adjusted HR 1.46, 95% CI 1.06-1.99) and major bleedings (PSM adjusted HR 1.73, 95% CI 1.09-2.76), resulting in a neutral effect on NACE (PSM adjusted HR 0.87, 95% CI 0.65-1.17). These results remained consistent across all subgroups., Conclusions: In patients with ACS undergoing percutaneous coronary intervention and receiving potent P2Y12 inhibitors, we observed a reduced risk of MACE and an increased risk of major bleedings at 1 year in patients treated with GPI. Although the routine use of GPI is currently not recommended, they might be considered in selected patients following a personalized balancing between ischaemic and bleeding risks., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Patients with heart failure (HF) remain often undertreated for multiple reasons, including treatment inertia, contraindications, and intolerance. The OPTIimal PHARMacological therapy for patients with Heart Failure (OPTIPHARM-HF) registry is designed to evaluate the prevalence of evidence-based medical treatment prescription and titration, as well as the causes of its underuse, in a broad real-world population of consecutive patients with HF across the whole ejection fraction spectrum and among different clinical phenotypes., Methods: The OPTIPHARM-HF registry (NCT06192524) is a prospective, multicenter, observational, national study of adult patients with symptomatic HF, as defined by current international guidelines, regardless of ejection fraction. Both outpatients and inpatients with chronic and acute decompensated HF will be recruited. The study will enroll up to 2500 patients with chronic HF at approximately 35 Italian HF centres. Patients will be followed for a maximum duration of 24 months. The primary objective of the OPTIPHARM-HF registry is to assess prescription and adherence to evidence-based guideline-directed medical therapy (GDMT) in patients with HF. The primary outcome is to describe the prevalence of GDMT use according to target guideline recommendation. Secondary objectives include implementation of comorbidity treatment, evaluation of sequence of treatment introduction and up-titration, description of GDMT implementation in the specific HF population, main causes of GDMT underuse, and assessment of cumulative rate of cardiovascular events., Conclusion: The OPTIPHARM-HF registry will provide important implications for improving patient care and adoption of recommended medical therapy into clinical practice among HF patients., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: In the last few years, percutaneous LAA occlusion (LAAO) has become a plausible alternative in atrial fibrillation (AF) patients with contraindications to anticoagulation therapy. Nevertheless, the optimal antiplatelet strategy following percutaneous LAAO remains to be defined., Methods: Studies comparing single antiplatelet therapy (SAPT) versus dual antiplatelet therapy (DAPT) following LAAO were systematically searched and screened. The outcomes of interest were ischemic stroke, device-related thrombus (DRT) and major bleeding. A random-effect meta-analysis was performed comparing outcomes in both groups. The moderator effect of baseline characteristics on outcomes was evaluated by univariate meta-regression analyses., Results: Sixteen observational studies with 3255 patients treated with antiplatelet therapy (SAPT, n = 1033; DAPT, n = 2222) after LAAO were included. Mean age was 74.5 ± 8.3 years, mean CHA 2 DS 2 -VASc and HAS-BLED scores were 4.3 ± 1.5 and 3.2 ± 1.0, respectively. At a weighted mean follow-up of 12.7 months, the occurrence of stroke (RR 1.33; 95% CI 0.64-2.77; p =.44), DRT (RR 1.52; 95% CI 0.90-2.58; p =.12), and the composite of stroke and DRT (RR 1.26; 95% CI 0.67-2.37; p =.47) did not differ significantly between SAPT and DAPT groups. The rate of major bleedings was also not different between groups (RR 1.41; 95% CI 0.64-3.12; p =.39)., Conclusions: Among AF patients at high bleeding risk undergoing percutaneous LAAO, a post-procedural minimalistic antiplatelet strategy with SAPT did not significantly differ from DAPT regimens regarding the rate of stroke, DRT and major bleeding., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Tako-Tsubo syndrome (TTS) presents as transient ventricular dysfunction, yet its underlying pathophysiology remains enigmatic. The prognosis of patients presenting with TTS appears to be impaired as compared to the general population and is similar to patients with acute coronary syndromes. Recent investigations have predominantly focused on elucidating therapeutic strategies associated with improved outcomes, particularly among post-menopausal female patients. Current evidence suggests that angiotensin-converting enzyme inhibitors (ACEi) may confer a survival advantage in TTS. Notably, ACEi emerges as the sole therapeutic modality demonstrating efficacy in both acute and chronic clinical courses of TTS. Despite this, the magnitude of survival benefit remains less pronounced than anticipated. This underscores the need for further research to explore additional therapeutic pathways and optimize management strategies for this unique patient cohort. Randomized clinical trials and meta-analysis are paramount in discerning the most effective therapeutic interventions aimed at enhancing survival and ameliorating outcomes in TTS. This review aims to comprehensively synthesize evidence pertaining to the prognostic implications of cardiovascular medications in TTS management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The quantification of stenosis severity from X-ray catheter angiography is a challenging task. Indeed, this requires to fully understand the lesion's geometry by analyzing dynamics of the contrast material, only relying on visual observation by clinicians. To support decision making for cardiac intervention, we propose a hybrid CNN-Transformer model for the assessment of angiography-based non-invasive fractional flow-reserve (FFR) and instantaneous wave-free ratio (iFR) of intermediate coronary stenosis. Our approach predicts whether a coronary artery stenosis is hemodynamically significant and provides direct FFR and iFR estimates. This is achieved through a combination of regression and classification branches that forces the model to focus on the cut-off region of FFR (around 0.8 FFR value), which is highly critical for decision-making. We also propose a spatio-temporal factorization mechanisms that redesigns the transformer's self-attention mechanism to capture both local spatial and temporal interactions between vessel geometry, blood flow dynamics, and lesion morphology. The proposed method achieves state-of-the-art performance on a dataset of 778 exams from 389 patients. Unlike existing methods, our approach employs a single angiography view and does not require knowledge of the key frame; supervision at training time is provided by a classification loss (based on a threshold of the FFR/iFR values) and a regression loss for direct estimation. Finally, the analysis of model interpretability and calibration shows that, in spite of the complexity of angiographic imaging data, our method can robustly identify the location of the stenosis and correlate prediction uncertainty to the provided output scores.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are new anti-hyperglycaemic drugs with proven cardiovascular (CV) benefit in diabetic and non-diabetic patients at high CV risk. Despite a neutral class effect on arrhythmia risk, data on semaglutide suggest a possible drug-specific benefit in reducing atrial fibrillation (AF) occurrence., Objective: To perform a meta-analysis of randomized clinical trials (RCTs) to assess the risk of incident AF in patients treated with semaglutide compared to placebo., Methods and Results: Ten RCTs were included in the analysis. Study population encompassed 12,651 patients (7285 in semaglutide and 5366 in placebo arms), with median follow-up of 68 months. A random effect meta-analytic model was adopted to pool relative risk (RR) of incident AF. Semaglutide reduces the risk of AF by 42% (RR .58, 95% CI .40-.85), with low heterogeneity across the studies (I 2 0%). At subgroup analysis, no differences emerged between oral and subcutaneous administration (oral: RR .53, 95% CI .23-1.24, I 2 0%; subcutaneous: RR .59, 95% CI .39-.91, I 2 0%; p-value .83). In addition, meta-regression analyses did not show any potential influence of baseline study covariates, in particular the proportion of diabetic patients (p-value .14) and body mass index (BMI) (p-value .60)., Conclusions: Semaglutide significantly reduces the occurrence of incident AF by 42% as compared to placebo in individuals at high CV risk, mainly affected by type 2 diabetes mellitus. This effect appears to be consistent independently of the route of administration of the drug (oral or subcutaneous), the presence of underlying diabetes and BMI., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background and Aims: Intracoronary pressure gradients and translesional flow patterns have been correlated with coronary plaque progression and lesion destabilization. In this study, we aimed to determine the relationship between endothelial shear stress and plaque progression and to evaluate the effect of shear forces on coronary plaque features., Methods: A systematic review was conducted in medical on-line databases. Selected were studies including human participants who underwent coronary anatomy assessment with computational fluid dynamics (CFD)-based wall shear stress (WSS) calculation at baseline with anatomical evaluation at follow-up. A total of six studies were included for data extraction and analysis., Results: The meta-analysis encompassed 31'385 arterial segments from 136 patients. Lower translesional WSS values were significantly associated with a reduction in lumen area (mean difference -0.88, 95% CI -1.13 to -0.62), an increase in plaque burden (mean difference 4.32, 95% CI 1.65 to 6.99), and an increase in necrotic core area (mean difference 0.02, 95% CI 0.02 to 0.03) at follow-up imaging. Elevated WSS values were associated with an increase in lumen area (mean difference 0.78, 95% CI 0.34 to 1.21) and a reduction in both fibrofatty (mean difference -0.02, 95% CI -0.03 to -0.01) and fibrous plaque areas (mean difference -0.03, 95% CI -0.03 to -0.03)., Conclusion: This meta-analysis shows that WSS parameters were related to vulnerable plaque features at follow-up. These results emphasize the impact of endothelial shear forces on coronary plaque growth and composition. Future studies are warranted to evaluate the role of WSS in guiding clinical decision-making., Competing Interests: Declaration of competing interest A. C. has consultancy agreements with Medyria and Nanoflex. B. S. received research grants to the institution from the OPO Foundation, the Iten-Kohaut Foundation, the German Center for Cardiovascular Research (DZHK), Boston Scientific, and Edwards Lifesciences and has received consulting and speaker fees from Boston Scientific and Abbott Vascular. B.S. has been supported by the H.H. Sheikh Khalifa bin Hamad Al-Thani Research Programme. The remaining authors have nothing to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Patients presenting with cardiogenic shock (CS) are at risk of developing mixed shock (MS), characterized by distributive-inflammatory phenotype. However, no objective definition exists for this clinical entity., Methods: We assessed the frequency, predictors, and prognostic relevance of MS complicating CS, based on a newly proposed objective definition. MS complicating CS was defined as an objective shock state secondary to both an ongoing cardiogenic cause and a distributive-inflammatory phenotype arising at least 12 hours after the initial CS diagnosis, as substantiated by predefined longitudinal changes in hemodynamics, clinical, and laboratory parameters., Results: Among 213 consecutive patients admitted at 2 cardiac intensive care units with CS, 13 with inflammatory-distributive features at initial presentation were excluded, leading to a cohort of 200 patients hospitalized with pure CS (67±13 years, 96% Society of Cardiovascular Angiography and Interventions CS stage class C or higher). MS complicating CS occurred in 24.5% after 120 (29-216) hours from CS diagnosis. Lower systolic arterial pressure ( P =0.043), hepatic injury ( P =0.049), and suspected/definite infection ( P =0.013) at CS diagnosis were independent predictors of MS development. In-hospital mortality (53.1% versus 27.8%; P =0.002) and hospital stay (21 [13-48] versus 17 [9-27] days; P =0.018) were higher in the MS cohort. At logistic multivariable analysis, MS diagnosis (odds ratio [OR], 3.00 [95% CI, 1.39-6.63]; P adj =0.006), age (OR, 1.06 [95% CI, 1.03-1.10] years; P adj <0.001), admission systolic arterial pressure <100 mm Hg (OR, 2.41 [95% CI, 1.19-4.98]; P adj =0.016), and admission serum creatinine (OR, 1.61 [95% CI, 1.19-2.26]; P adj =0.003) conferred higher odds of in-hospital death, while early temporary mechanical circulatory support was associated with lower in-hospital death (OR, 0.36 [95% CI, 0.17-0.75]; P adj =0.008)., Conclusions: MS complicating CS, objectively defined leveraging on longitudinal changes in distributive and inflammatory features, occurs in one-fourth of patients with CS, is predicted by markers of CS severity and inflammation at CS diagnosis, and portends higher hospital mortality., Competing Interests: None.

Background: The impact of statin therapy on cardiovascular outcomes after ST-elevation acute myocardial infarction (STEMI) in real- world patients is understudied., Aims: To identify predictors of low adherence and discontinuation to statin therapy within 6 months after STEMI and to estimate their impact on cardiovascular outcomes at one year follow-up., Methods: We evaluated real-world adherence to statin therapy by comparing the number of bought tablets to the expected ones at 1 year follow-up through pharmacy registries. A total of 6043 STEMI patients admitted from 2012 to 2017 were enrolled in the FAST STEMI registry and followed up for 4,7 ± 1,6 years; 304 patients with intraprocedural and intrahospital deaths were excluded. The main outcomes evaluated were all-cause death, cardiovascular death, myocardial infarction, major and minor bleeding events, and ischemic stroke. The compliance cut-off chosen was 80% as mainly reported in literature., Results: From a total of 5744 patients, 418 (7,2%) patients interrupted statin therapy within 6 months after STEMI, whereas 3337 (58,1%) presented >80% adherence to statin therapy. Statin optimal adherence (>80%) resulted as protective factor towards both cardiovascular (0.1% vs 4.6%; AdjHR 0.025, 95%CI 0.008-0.079, p < 0.001) and all-cause mortality (0.3% vs 13.4%; Adj HR 0.032, 95%CI 0.018-0.059, p < 0.001) at 1 year follow-up. Further, a significant reduction of ischemic stroke incidence (1% vs 2.5%, p = 0.001) was seen in the optimal adherent group. Statin discontinuation within 6 months after STEMI showed an increase of both cardiovascular (5% vs 1.7%; AdjHR 2.23; 95%CI 1.37-3.65; p = 0,001) and all-cause mortality (14.8% vs 5.1%, AdjHR 2.32; 95%CI 1.73-3.11; p 〈0,001) at 1 year follow-up. After multivariate analysis age over 75 years old, known ischemic cardiopathy and female gender resulted as predictors of therapy discontinuation. Age over 75 years old, chronic kidney disease, previous atrial fibrillation, vasculopathy, known ischemic cardiopathy were found to be predictors of low statin adherence., Conclusions: n our real-world registry low statin adherence and discontinuation therapy within 6 months after STEMI were independently associated to an increase of cardiovascular and all-cause mortality at 1 year follow-up. Low statin adherence led to higher rates of ischemic stroke., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: To perform a systematic review and meta-analysis of studies investigating the diagnostic value of cardiac magnetic resonance (CMR) features for arrhythmic risk stratification in mitral valve prolapse (MVP) patients., Materials and Methods: EMBASE, PubMed/MEDLINE, and CENTRAL were searched for studies reporting MVP patients who underwent CMR with assessment of: left ventricular (LV) size and function, mitral regurgitation (MR), prolapse distance, mitral annular disjunction (MAD), curling, late gadolinium enhancement (LGE), and T1 mapping, and reported the association with arrhythmia. The primary endpoint was complex ventricular arrhythmias (co-VAs) as defined by any non-sustained ventricular tachycardia, sustained ventricular tachycardia, ventricular fibrillation, or aborted sudden cardiac death. Meta-analysis was performed when at least three studies investigated a CMR feature. PROSPERO registration number: CRD42023374185., Results: The meta-analysis included 11 studies with 1278 patients. MR severity, leaflet length/thickness, curling, MAD distance, and mapping techniques were not meta-analyzed as reported in < 3 studies. LV end-diastolic volume index, LV ejection fraction, and prolapse distance showed small non-significant effect sizes. LGE showed a strong and significant association with co-VA with a LogORs of 2.12 (95% confidence interval (CI): [1.00, 3.23]), for MAD the log odds-ratio was 0.95 (95% CI: [0.30, 1.60]). The predictive accuracy of LGE was substantial, with a hierarchical summary ROC AUC of 0.83 (95% CI: [0.69, 0.91]) and sensitivity and specificity rates of 0.70 (95% CI: [0.41, 0.89]) and 0.80 (95% CI: [0.67, 0.89]), respectively., Conclusions: Our study highlights the role of LGE as the key CMR feature for arrhythmia risk stratification in MVP patients. MAD might complement arrhythmic risk stratification., Clinical Relevance Statement: LGE is a key factor for arrhythmogenic risk in MVP patients, with additional contribution from MAD. Combining MRI findings with clinical characteristics is critical for evaluating and accurately stratifying arrhythmogenic risk in MVP patients., Key Points: MVP affects 2-3% of the population, with some facing increased risk for arrhythmia. LGE can assess arrhythmia risk, and MAD may further stratify patients. CMR is critical for MVP arrhythmia risk stratification, making it essential in a comprehensive evaluation., (© 2024. The Author(s).)

Objectives: To compare dual antiplatelet therapy (DAPT) de-escalation with five alternative DAPT strategies in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI)., Design: We conducted a systematic review and network meta-analysis (NMA). Parallel-arm randomised controlled trials (RCTs) comparing DAPT strategies were included and arms of interest were compared via NMA. Partial ranking of each identified arm and for each investigated endpoint was also performed., Setting and Participants: Adult patients with ACS (≥18 years) undergoing PCI with indications for DAPT., Search Methods: A comprehensive search covered several databases (PubMed, Embase, Cochrane Central, MEDLINE, Conference Proceeding Citation Index-Science) from inception to 15 October 2023. Medical subject headings and keywords related to ACS, PCI and DAPT interventions were used. Reference lists of included studies were screened. Clinical trials registers were searched for ongoing or unpublished trials., Interventions: Six strategies were assessed: T1 arm: acetylsalicylic acid (ASA) and prasugrel for 12 months; T2 arm: ASA and low-dose prasugrel for 12 months; T3 arm: ASA and ticagrelor for 12 months; T4 arm: DAPT de-escalation (ASA+P2Y12 inhibitor for 1-3 months, then single antiplatelet therapy with potent P2Y12 inhibitor or DAPT with clopidogrel); T5 arm: ASA and clopidogrel for 12 months; T6 arm: ASA and clopidogrel for 3-6 months., Main Outcome Measures: Primary outcome: Cardiovascular mortality., Secondary Outcomes: bleeding events (all, major, minor), stent thrombosis (ST), stroke, myocardial infarction (MI), all-cause mortality, major adverse cardiovascular events (MACE)., Results: 23 RCTs (75 064 patients with ACS) were included. No differences in cardiovascular mortality, all-cause death, recurrent MI or MACE were found when the six strategies were compared, although with different levels of certainty of evidence. ASA and clopidogrel for 12 or 3-6 months may result in a large increase of ST risk versus ASA plus full-dose prasugrel (OR 2.00, 95% CI 1.14 to 3.12, and OR 3.42, 95% CI 1.33 to 7.26, respectively; low certainty evidence for both comparisons). DAPT de-escalation probably results in a reduced risk of all bleedings compared with ASA plus full-dose 12-month prasugrel (OR 0.49, 95% CI 0.26 to 0.81, moderate-certainty evidence) and ASA plus 12-month ticagrelor (OR 0.52, 95% CI 0.33 to 0.75), while it may not increase the risk of ST. ASA plus 12-month clopidogrel may reduce all bleedings versus ASA plus full-dose 12-month prasugrel (OR 0.66, 95% CI 0.42 to 0.94, low certainty) and ASA plus 12-month ticagrelor (OR 0.70, 95% CI 0.52 to 0.89)., Conclusions: DAPT de-escalation and ASA-clopidogrel regimens may reduce bleeding events compared with 12 months ASA and potent P2Y12 inhibitors. 3-6 months or 12-month aspirin-clopidogrel may increase ST risk compared with 12-month aspirin plus potent P2Y12 inhibitors, while DAPT de-escalation probably does not., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We evaluated the potential benefits of renin-angiotensin-aldosterone system inhibitors (RAASi) in patients with left ventricular assist device support., Methods and Results: A total of 165 consecutive patients undergoing left ventricular assist device implant and alive at 6-month on support were studied. RAASi status after 6-month visit along with clinical reasons for nonprescription/uptitration were retrospectively assessed. The primary outcome was a composite of heart failure hospitalization or cardiovascular death between 6 and 24 months after left ventricular assist device implant. Remodeling and hemodynamic outcomes were explored by studying the association of RAASi new prescription/uptitration versus unmodified therapy at 6-month visit with the change in echocardiographic parameters and hemodynamics between 6 and 18 months. After the 6-month visit, 76% of patients were on RAASi. Patients' characteristics among those receiving and not receiving RAASi were mostly similar. Of 85 (52%) patients without RAASi new prescription/uptitration at 6-month visit, 62% had no apparent clinical reason. RAASi were independently associated with the primary outcome (adjusted hazard ratio, 0.31 [95% CI, 0.16-0.69]). The baseline rates of optimal echocardiographic profile (neutral interventricular septum, mitral regurgitation less than mild, and aortic valve opening) and hemodynamic profile (cardiac index ≥2.2 L/min per m 2 , wedge pressure <18 mm Hg, and right atrial pressure <12 mm Hg) were similar between groups. At 18 months, patients receiving RAASi new prescription/uptitration at 6 months had higher rates of optimal hemodynamic profile (57.5% versus 37.0%; P =0.032) and trends for higher rates of optimal echocardiographic profile (39.6% versus 22.9%; P =0.055) compared with patients with 6-month unmodified therapy. Optimal 18-month hemodynamic and echocardiographic profiles were associated with the primary outcome (log-rank=0.022 and log-rank=0.035, respectively)., Conclusions: RAASi are associated with improved outcomes and improved hemodynamics among mechanically unloaded patients.

Cardiac resynchronization therapy (CRT) significantly improves clinical outcomes in patients with ventricular systolic dysfunction and dyssynchrony. Biventricular pacing (BVP) has a class IA recommendation for patients with symptomatic heart failure with reduced ejection fraction (HFrEF) and left bundle branch block (LBBB). However, approximately 30% of patients have a poor therapeutic response and do not achieve real clinical benefit. Pre-implant imaging, together with tailored programming and dedicated device algorithms, have been proposed as possible tools to improve success rate but have shown inconsistent results. Over the last few years, conduction system pacing (CSP) is becoming a real and attractive alternative to standard BVP as it can restore narrow QRS in patients with bundle branch block (BBB) by stimulating and recruiting the cardiac conduction system, thus ensuring true resynchronization. It includes His bundle pacing (HBP) and left bundle branch area pacing (LBBAP). Preliminary data coming from small single-center experiences are very promising and have laid the basis for currently ongoing randomized controlled trials comparing CSP with BVP. The purpose of this review is to delve into the emerging role of CSP as an alternative method of achieving CRT. After framing CSP in a historical perspective, the pathophysiological rationale and available clinical evidence will be examined, and crucial technical aspects will be discussed. Finally, evidence gaps and future perspectives on CSP as a technique of choice to deliver CRT will be summarized.

Introduction: Among different coronary stents implanted in High Bleeding Risk (HBR) patients with an indication for short antiplatelet therapy, no comparisons in terms of efficacy have been provided., Methods: A Network Meta Analysis was performed including all randomized controlled trials comparing different coronary stents evaluated in HBR patients. Major Adverse Cardiovascular Events (MACEs) as defined by each included trial were the primary end point, whereas TLR (target lesion revascularization), TVR (target vessel revascularization), stent thrombosis and total and major (BARC3-5) bleedings were the secondary ones., Results: A total of four studies (ONYX ONE, LEADERS FREE, SENIOR and HBR in BIO-RESORT) including 6637 patients were analyzed with different kind of stents and dual antiplatelet therapy (DAPT) length (1 or 6 months) on 12 months follow-up. About one-third of these patients were defined HBR due to indication for oral anticoagulation. All drug eluting stents (DESs) reduced risk of MACE compared to Bare Metal Stents (BMSs) when followed by a 1-month DAPT. At SUCRA analysis, Orsiro was the device with the highest probability of performing best. Rates of TLR and TVR were significantly lower when using Resolute Onyx, Synergy and BioFreedom stents in comparison to BMS when followed by 1-month DAPT, with Synergy ranking best. Synergy also showed a significantly lower number of stent thrombosis compared to BMS (RR 0.28, 95% CI 0.06-0.93), while Orsiro and Resolute Integrity showed the highest probability of performing best., Conclusion: In HBRs patients, all DESs were superior to BMSs in terms of efficacy and safety. Among DESs, Orsiro was the one with the highest ranking in terms of MACE, mainly driven by a reduced incidence of repeated revascularization and stent thrombosis., (© 2024 Wiley Periodicals LLC.)

Background and Objective: In everyday clinical practice, medical decision is currently based on clinical guidelines which are often static and rigid, and do not account for population variability, while individualized, patient-oriented decision and/or treatment are the paradigm change necessary to enter into the era of precision medicine. Most of the limitations of a guideline-based system could be overcome through the adoption of Clinical Decision Support Systems (CDSSs) based on Artificial Intelligence (AI) algorithms. However, the black-box nature of AI algorithms has hampered a large adoption of AI-based CDSSs in clinical practice. In this study, an innovative AI-based method to compress AI-based prediction models into explainable, model-agnostic, and reduced decision support systems (NEAR) with application to healthcare is presented and validated., Methods: NEAR is based on the Shapley Additive Explanations framework and can be applied to complex input models to obtain the contributions of each input feature to the output. Technically, the simplified NEAR models approximate contributions from input features using a custom library and merge them to determine the final output. Finally, NEAR estimates the confidence error associated with the single input feature contributing to the final score, making the result more interpretable. Here, NEAR is evaluated on a clinical real-world use case, the mortality prediction in patients who experienced Acute Coronary Syndrome (ACS), applying three different Machine Learning/Deep Learning models as implementation examples., Results: NEAR, when applied to the ACS use case, exhibits performances like the ones of the AI-based model from which it is derived, as in the case of the Adaptive Boosting classifier, whose Area Under the Curve is not statistically different from the NEAR one, even the model's simplification. Moreover, NEAR comes with intrinsic explainability and modularity, as it can be tested on the developed web application platform (https://neardashboard.pythonanywhere.com/)., Conclusions: An explainable and reliable CDSS tailored to single-patient analysis has been developed. The proposed AI-based system has the potential to be used alongside the clinical guidelines currently employed in the medical setting making them more personalized and dynamic and assisting doctors in taking their everyday clinical decisions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The relationship between epicardial adipose tissue (EAT) and atrial fibrillation (AF) has gained interest in recent years. The previous literature on the topic presents great heterogeneity, focusing especially on computed tomography imaging. The aim of the present study is to determine whether an increased volume of left atrial (LA) EAT evaluated at routine pre-procedural cardiac magnetic resonance imaging (MRI) relates to AF recurrences after catheter ablation. A total of 50 patients undergoing AF cryoballoon ablation and pre-procedural cardiac MRI allowing quantification of LA EAT were enrolled. In one patient, the segmentation of LA EAT could not be achieved. After a median follow-up of 16.0 months, AF recurrences occurred in 17 patients (34%). The absolute volume of EAT was not different in patients with and without AF recurrences (10.35 mL vs. 10.29 mL; p -value = 0.963), whereas the volume of EAT indexed on the LA volume (EATi) was lower, albeit non-statistically significant, in patients free from arrhythmias (12.77% vs. 14.06%; p -value = 0.467). The receiver operating characteristic curve testing the ability of LA EATi to predict AF recurrence after catheter ablation showed sub-optimal performance (AUC: 0.588). The finest identified cut-off of LA EATi was 10.65%, achieving a sensitivity of 0.5, a specificity of 0.82, a positive predictive value of 0.59 and a negative predictive value of 0.76. Patients with values of LA EATi lower than 10.65% showed greater survival, free from arrhythmias, than patients with values above this cut-off (84% vs. 48%; p -value = 0.04). In conclusion, EAT volume indexed on the LA volume evaluated at cardiac MRI emerges as a possible independent predictor of arrhythmia recurrence after AF cryoballoon ablation. Nevertheless, prospective studies are needed to confirm this finding and eventually sustain routine EAT evaluation in the management of patients undergoing AF catheter ablation.

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., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Ultrathin-strut drug-eluting stents (DES) have been related to potential improvement in stent-related outcomes compared with thicker-struts DES. However, comparisons among different ultrathin devices are lacking. All randomized controlled trials comparing ultrathin (struts thickness <70 µm) and thicker-struts DESs in an all-comers population were included. Target lesion failure (TLF), as defined by included trials, at 1-year follow-up was the primary end point. Overall mortality, myocardial infarction, target lesion revascularization (TLR), and stent thrombosis were the secondary end points. Arms of included trials were compared using network meta-analysis. Nine studies encompassing 20,081 patients were included, of which 9,509 patients had an ultrathin DES: Orsiro (evaluated in 7 arms with 8,086 patients), MiStent (1 arm with 703 patients), or Supraflex (1 arm with 720 patients). At 1-year follow-up, no significant differences were noted for TLF among these ultrathin DES. In particular, Orsiro was associated with a similar risk of TLF compared with Supraflex (risk rate 1.07, 95% confidence interval 0.59 to 1.78) and showed the highest probability of performing best in terms of TLF, myocardial infarction, and TLR. Ultrathin DES are all associated with a comparable risk of TLF compared with thicker-strut DES. In terms of TLR and TLF risk, Orsiro was the one with the highest probability of best performances, either compared with other ultrathin DES or to devices with thicker struts., Competing Interests: Declaration of competing interest Dr. Pilgrim received research grants to the institution from Biotronik, Edwards Lifesciences, and Boston Scientific, and speaker fees/consultancy from Biotronik, Boston Scientific, Edwards Lifesciences, Abbott, Medtronic, and HighLife SAS. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: Percutaneous stellate ganglion block (PSGB) through single-bolus injection and thoracic epidural anaesthesia (TEA) have been proposed for the acute management of refractory ventricular arrhythmias (VAs). However, data on continuous PSGB (C-PSGB) are scant. The aim of this study is to report our dual-centre experience with C-PSGB and to perform a systematic review on C-PSGB and TEA., Methods and Results: Consecutive patients receiving C-PSGB at two centres were enrolled. The systematic literature review follows the latest Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Our case series (26 patients, 88% male, 60 ± 16 years, all with advanced structural heart disease, left ventricular ejection fraction 23 ± 11%, 32 C-PSGBs performed, with a median duration of 3 days) shows that C-PSGB is feasible and safe and leads to complete VAs suppression in 59% and to overall clinical benefit in 94% of cases. Overall, 61 patients received 68 C-PSGBs and 22 TEA, with complete VA suppression in 63% of C-PSGBs (61% of patients). Most TEA procedures (55%) were performed on intubated patients, as opposed to 28% of C-PSGBs (P = 0.02); 63% of cases were on full anticoagulation at C-PSGB, none at TEA (P < 0.001). Ropivacaine and lidocaine were the most used drugs for C-PSGB, and the available data support a starting dose of 12 and 100 mg/h, respectively. No major complications occurred, yet TEA discontinuation rate due to side effects was higher than C-PSGB (18 vs. 1%, P = 0.01)., Conclusion: Continuous PSGB seems feasible, safe, and effective for the acute management of refractory VAs. The antiarrhythmic effect may be accomplished with less concerns for concomitant anticoagulation compared with TEA and with a lower side-effect related discontinuation rate., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Objectives: Atrial fibrillation (AF) results in systemic hemodynamic perturbations which impact cerebral circulation, possibly contributing to the development of dementia. However, evidence documenting effects in cerebral perfusion is scarce. The aim of this study is to provide a quantitative characterization of the magnitude and time course of the cerebral hemodynamic response to the short hypotensive events associated with long R-R intervals, as detected by near-infrared spectroscopy (NIRS). Materials and Methods: Cerebral NIRS signals and arterial blood pressure were continuously recorded along with an electrocardiogram in twelve patients with AF undergoing elective electrical cardioversion (ECV). The top 0.5-2.5% longest R-R intervals during AF were identified in each patient and used as triggers to carry out the triggered averaging of hemodynamic signals. The average curves were then characterized in terms of the latency, magnitude, and duration of the observed effects, and the possible occurrence of an overshoot was also investigated. Results: The triggered averages revealed that long R-R intervals produced a significant drop in diastolic blood pressure (-13.7 ± 6.1 mmHg) associated with an immediate drop in cerebral blood volume (THI: -0.92 ± 0.46%, lasting 1.9 ± 0.8 s), followed by a longer-lasting decrease in cerebral oxygenation (TOI: -0.79 ± 0.37%, lasting 5.2 ± 0.9 s, p < 0.01). The recovery of the TOI was generally followed by an overshoot (+1.06 ± 0.12%). These effects were progressively attenuated in response to R-R intervals of a shorter duration. Conclusions: Long R-R intervals cause a detectable and consistent cerebral hemodynamic response which concerns both cerebral blood volume and oxygenation and outlasts the duration of the systemic perturbation. These effects are compatible with the activation of dynamic autoregulatory mechanisms in response to the hypotensive stimulus.

Background: Diagnosis of pericarditis may be challenging because not all patients meet the conventional criteria. An overlooked diagnosis implies a longer course of symptoms and an increased risk of recurrences. C-reactive protein (CRP), widely used as an inflammation marker, has some limitations. This study aimed to assess the usefulness and prognostic value of INFLA-score, a validated index assessing low-grade inflammation, in the definite diagnosis of pericarditis., Methods: Patients with suspected pericarditis were included. The INFLA-score was computed based on white blood cells and platelet count, neutrophil-to-lymphocyte ratio, and CRP, ranging from -16 to +16. An INFLA-score > 0 was considered positive for the presence of pericardial inflammation. The primary end point was the association of INFLA-score with diagnosis of pericarditis according to conventional criteria. The recurrence of pericarditis at 6 months was the secondary end point., Results: A total of 202 patients were included, aged 47 ± 17 years, and 57% were females. Among 72 (36%) patients with a diagnosis of pericarditis, an INFLA-score > 0 was observed in 86% (vs. 36%, p < 0.001), abnormal CRP in 42% (vs. 10%, p < 0.001), pericardial effusion in 44% (vs. 19%, p < 0.001), abnormal electrocardiogram in 56% (vs. 24%, p < 0.001), and rubs in 5% (vs. 0.1%, p = 0.072). INFLA-score > 0 had the strongest predictive value for the diagnosis of pericarditis (hazard ratio 8.48, 95% confidence interval [CI] 3.39-21.21), with 86% sensitivity and 64% specificity, as opposed to CRP (hazard ratio 1.72, non-significant 95% CI 0.69-4.29). Recurrent pericarditis at 6 months was more frequent in patients with a positive INFLA-score (37% vs. 8%, p < 0.001, rate ratio 4.15, 95% CI 2.81-6.12). In patients with normal CRP, INFLA-score-confirmed ongoing inflammation in 78% of the cases. Compared with the conventional criteria, the INFLA-score had the highest accuracy (area under the curve = 0.82). Different cutoffs were valuable to rule out (INFLA-score > 0, sensitivity 86%, and negative likelihood ratio 0.22) or rule in (INFLA-score ≥ 10, specificity 97%, and positive likelihood ratio 13) the diagnosis., Conclusions: The INFLA-score is a useful diagnostic tool to assess the probability of pericarditis, with a strong prognostic value for further recurrences, outperforming CRP., Competing Interests: Declarations of interest None., (Copyright © 2024 Hellenic Society of Cardiology. Published by Elsevier Inc. All rights reserved.)

Background: The prognostic impact of catheter ablation (CA) of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients has not yet been satisfactorily elucidated., Objectives: The aim of the study was to assess the impact of CA of AF on clinical outcomes in a large cohort of HCM patients., Methods: In this retrospective multicenter study, 555 HCM patients with AF were enrolled, 140 undergoing CA and 415 receiving medical therapy. 1:1 propensity score matching led to the inclusion of 226 patients (113 medical group, 113 intervention group) in the final analysis. The primary outcome was a composite of all-cause mortality, heart transplant and acute heart failure exacerbations. Secondary outcomes included AF recurrence and transition to permanent AF. Additionally, an inverse probability weighted (IPW) model was examined., Results: At propensity score matching analysis, after a median follow-up of 58.1 months, the primary endpoint occurred in 29 (25.7%) patients in intervention group vs 42 (37.2%) in medical group ( P  = 0.9). Thromboembolic strokes and major arrhythmic events in intervention vs medical group were 9.7% vs 7.1% ( P  = 0.144) and 4.4 vs 8.0% ( P  = 0.779), respectively. Fewer patients in intervention vs medical group experienced AF recurrences (63.7% vs 84.1%, P  = 0.001) and transition to permanent AF pattern (20.4% vs 33.6%, P  = 0.026). IPW analysis showed consistent results. Severe complications related to CA were uncommon (0.7%)., Conclusions: After 5 years of follow-up, CA did not improve major adverse cardiac outcomes in a large cohort of patients with HCM and AF. Nevertheless, CA seems to facilitate the maintenance of sinus rhythm and slow the progression to permanent AF, without significant safety concerns., Competing Interests: Prof Olivotto has received research grants from: BMS-Myokardia, Cytokinetics, Boston Scientific, Amicus, Sanofi Genzyme, Shire Takeda, Menarini International, Bayer, and Chiesi, Tenaya; and is on the advisory board for BMS-Myokardia, Cytokinetics, Amicus, Sanofi Genzyme, Chiesi, Tenaya, and Rocket Pharma. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background and Aims: An electrical storm (ES) is a clinical emergency with a paucity of established treatment options. Despite initial encouraging reports about the safety and effectiveness of percutaneous stellate ganglion block (PSGB), many questions remained unsettled and evidence from a prospective multicentre study was still lacking. For these purposes, the STAR study was designed., Methods: This is a multicentre observational study enrolling patients suffering from an ES refractory to standard treatment from 1 July 2017 to 30 June 2023. The primary outcome was the reduction of treated arrhythmic events by at least 50% comparing the 12 h following PSGB with the 12 h before the procedure. STAR operators were specifically trained to both the anterior anatomical and the lateral ultrasound-guided approach., Results: A total of 131 patients from 19 centres were enrolled and underwent 184 PSGBs. Patients were mainly male (83.2%) with a median age of 68 (63.8-69.2) years and a depressed left ventricular ejection fraction (25.0 ± 12.3%). The primary outcome was reached in 92% of patients, and the median reduction of arrhythmic episodes between 12 h before and after PSGB was 100% (interquartile range -100% to -92.3%). Arrhythmic episodes requiring treatment were significantly reduced comparing 12 h before the first PSGB with 12 h after the last procedure [six (3-15.8) vs. 0 (0-1), P < .0001] and comparing 1 h before with 1 h after each procedure [2 (0-6) vs. 0 (0-0), P < .001]. One major complication occurred (0.5%)., Conclusions: The findings of this large, prospective, multicentre study provide evidence in favour of the effectiveness and safety of PSGB for the treatment of refractory ES., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The reduction of low-density lipoprotein cholesterol (LDL-C) with evolocumab, a fully human monoclonal antibody inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9i), reduces the risk of major adverse cardiovascular events in patients with established atherosclerotic cardiovascular disease (ASCVD) with a prior MI, prior stroke, or symptomatic peripheral artery disease, with no offsetting safety concerns. The effect of evolocumab on CV outcomes in lower risk patients without a history of MI or stroke has not been explored., Study Design: VESALIUS-CV is a randomized, double-blind, placebo-controlled, global clinical trial designed to evaluate the effect of evolocumab on the risk of major cardiovascular events in patients at high cardiovascular risk but without a prior ischemic event. The study population consists of 12,301 patients with atherosclerosis or high-risk diabetes mellitus without a prior MI or stroke; an LDL-C ≥ 90 mg/dL, or non-high-density lipoprotein cholesterol (non-HDL-C) ≥ 120 mg/dL, or apolipoprotein B ≥ 80 mg/dL; and treated with optimized lipid-lowering therapy. Patients were randomized in a 1:1 ratio to evolocumab 140 mg subcutaneously every 2 weeks or matching placebo. The primary efficacy objective is to assess whether evolocumab reduces the risk of the dual primary composite endpoints of coronary heart disease (CHD) death, myocardial infarction (MI), or ischemic stroke (triple primary endpoint) and of CHD death, MI, ischemic stroke, or ischemia-driven arterial revascularization (quadruple primary endpoint). Recruitment began in June 2019 and completed in November 2021. The trial is planned to continue until at least 751 patients experience an adjudicated triple endpoint, at least 1254 experience an adjudicated quadruple endpoint, and the median follow-up is ≥4.5 years., Conclusion: VESALIUS-CV will determine whether the addition of evolocumab to optimized lipid-lowering therapy reduces cardiovascular events in patients at high cardiovascular risk without a prior MI or stroke., Trial Registration: NCT03872401., Competing Interests: Disclosures Drs. Bohula, Giugliano, Marston, Murphy and Sabatine are members of the TIMI Study Group. The TIMI Study Group reports grant support through Brigham and Women's Hospital from Abbott, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc., AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Inc., Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Siemens Healthcare Diagnostics, Inc., Softcell Medical Limited, Verve Therapeutics, Zora Biosciences. Dr. Bohula reports personal fees from Kowa, Novo Nordisk, Servier and Esperion. Dr. Marston reports no personal fees. Dr. Leiter reports personal fees from Amarin, Amgen, AstraZeneca, HLS, Kowa, Merck, Pfizer, and Sanofi. Dr. Bhatia, Dr. Wang and Ms. Elliott-Davey are employees and stockholders of Amgen. Dr. Ruzza is former Amgen employee and stockholder, has a pending patent application PCT/US2021/034489 on PCSK9 inhibitors and methods of use thereof to treat cholesterol-related disorders, and is currently GSK employee and stockholder. Dr. Giugliano reports personal fees from Amgen, Daiichi-Sankyo, Dr. Reddy's Laboratories, Inventiva Pharma, Medical Education Resources, Pfizer, Sanofi, SUMMEET. Dr. Sabatine reports personal fees from Amgen; Anthos Therapeutics; AstraZeneca; Beren Therapeutics; Boehringer Ingelheim; Dr. Reddy's Laboratories; Fibrogen; Intarcia; Merck; Moderna; Novo Nordisk; Precision BioSciences; Silence Therapeutics., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: Hypoperfusion portends adverse outcomes in acute heart failure (AHF). The gradient between end-organ inflow and outflow pressures may more closely reflect hypoperfusion than mean arterial pressure (MAP) alone. The aim of this study was to investigate organ perfusion pressure (OPP), calculated as MAP minus central venous pressure (CVP), as a prognostic marker in AHF., Methods and Results: The Sodium NItroPrusside Treatment in Acute Heart Failure (SNIP)-AHF study was a multicentre retrospective cohort study of 200 consecutive patients hospitalized for AHF treated with sodium nitroprusside. Only patients with both MAP and invasive CVP data available from the SNIP-AHF cohort were included in this analysis. The primary endpoint was to assess OPP as a predictor of worsening heart failure (WHF), defined as the worsening of signs and symptoms of heart failure leading to intensification of therapy at 48 h. One hundred and forty-six patients fulfilling the inclusion criteria were included [mean age: 61.1 ± 13.5 years, 32 (21.9%) females; mean body mass index: 26.2 ± 11.7 kg/m2; mean left ventricular ejection fraction: 23.8%±11.4%, mean MAP: 80.2 ± 13.2 mmHg, and mean CVP: 14.0 ± 6.1 mmHg]. WHF occurred in 14 (9.6%) patients. At multivariable models including hemodynamic variables (OPP, shock index, and CVP), OPP at admission was the best predictor of WHF at 48 h [OR 0.91 (95% confidence interval 0.86-0.96), P-value = 0.001] with an optimal cut-off value of 67.5 mmHg (specificity 47.3%, sensitivity 100%, and AUC 0.784 ± 0.054). In multivariable models, including univariable significant parameters available at first bedside assessment, namely New York Heart Association functional class, OPP, shock index, CVP, and left ventricular end-diastolic diameter, OPP consistently and significantly predicted WHF at 48 h., Conclusion: In this retrospective analysis on patients hospitalized for AHF treated with sodium nitroprusside, on-admission OPP significantly predicted WHF at 48 h with high sensitivity., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Artificial intelligence (AI) has shown promise in the early detection of various cardiac conditions from a standard 12-lead electrocardiogram (ECG). However, the ability of AI to identify abnormalities from single-lead recordings across a range of pathological conditions remains to be systematically investigated. This study aims to assess the performance of a convolutional neural network (CNN) using a single-lead (D1) rather than a standard 12-lead setup for accurate identification of ECG abnormalities., Methods: We designed and trained a lightweight CNN to identify 20 different cardiac abnormalities on ECGs, using data from the PTB-XL dataset. With a relatively simple architecture, the network was designed to accommodate different combinations of leads as input (<100,000 learnable parameters). We compared various lead setups such as the standard 12-lead, D1 alone, and D1 paired with an additional lead., Results: This has been corrected to “The CNN based on single-lead ECG (D1) achieved satisfactory performance compared to the standard 12-lead framework (average percentage AUC difference: −8.7%). Notably, for certain diagnostic classes, there was no difference in the diagnostic AUC between the single-lead and the standard 12-lead setups. When a second lead was detected in the CNN in addition to D1, the AUC gap was further reduced to an average percentage difference of -2.8% compared with that of the standard 12-lead setup., Conclusions: A relatively lightweight CNN can predict different classes of cardiac abnormalities from D1 alone and the standard 12-lead ECG. Considering the growing availability of wearable devices capable of recording a D1-like single-lead ECG, we discuss how our findings contribute to the foundation of a large-scale screening of cardiac abnormalities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Saglietto, Baccega, Esposito, Anselmino, Dusi, Fiandrotti and De Ferrari.)

Background: Impact of gender on heart remodeling after acute coronary syndrome (ACS) and consequently on development of heart failure (HF) remains to be elucidated., Methods: CORALYS is a multicenter, retrospective, observational registry enrolling consecutive patients admitted for ACS and treated with percutaneous coronary intervention. HF hospitalization was the primary endpoint while all-cause mortality and the composite endpoint of incidence of first HF hospitalization and cardiovascular mortality were the secondary ones., Results: Among 14,699 patients enrolled in CORALYS registry, 4578 (31%) were women and 10,121 (69%) males. Women were older, had more frequently hypertension and diabetes and less frequently smoking habit. History of myocardial infarction (MI), STEMI at admission and multivessel disease were less common in women. After median follow up of 2.9 ± 1.8 years, women had higher incidence of primary and secondary endpoints and female sex was an independent predictor of HF hospitalization (HR 1.26;1.05-1.50; p = 0.011) and cardiovascular death/HF hospitalization (HR 1.18;1.02-1.37; p = 0.022). At multivariable analysis women and men share as predictors of HF diabetes, history of cancer, chronic kidney disease, atrial fibrillation, complete revascularization and left ventricular ejection fraction. Chronic obstructive pulmonary disease (HR 2.34;1.70-3.22, p < 0.001) and diuretics treatment (HR 1.61;1.27-2.04, p < 0.001) were predictor of HF in men, while history of previous MI (HR 1.46;1.08-1.97, p = 0.015) and treatment with inhibitors of renin-angiotensin system (HR 0.69;0,49-0.96 all 95% CI, p = 0.030) in women., Conclusions: Women are at increased risk of HF after ACS and gender seems to be an outcome-modifier of the relationship between a variable and primary outcome., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: In FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), during a median follow-up of 2.2 years, risk reduction for major adverse cardiovascular event with evolocumab was greater in patients with multivessel disease (MVD). The FOURIER Open-Label Extension (FOURIER-OLE) provides an additional median follow-up of 5 years., Objectives: The purpose of this study was to assess the long-term benefit of evolocumab in patients with and without MVD., Methods: FOURIER randomized 27,564 patients to evolocumab vs placebo; 6,635 entered FOURIER-OLE. Patients with coronary artery disease were categorized based on the presence of MVD (≥40% stenosis in ≥2 large vessels). The primary endpoint was cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization; the key secondary endpoint was cardiovascular death, myocardial infarction, or stroke., Results: Of 23,656 patients in FOURIER with coronary artery disease, 25.4% had MVD; 5,887 patients continued into FOURIER-OLE. The risk reduction with initial allocation to evolocumab tended to be greater in patients with MVD than in those without: 23% (HR: 0.77 [95% CI: 0.68-0.87]) vs 11% (HR: 0.89 [95% CI: 0.82-0.96]) for the primary and 31% (HR: 0.69 [95% CI: 0.59-0.81]) vs 15% (HR: 0.85 [95% CI: 0.77-0.94]) for the key secondary endpoints (P interaction = 0.062 and P interaction = 0.031, respectively). The magnitude of benefit tended to grow during the first several years, reaching 37% to 38% reductions in risk in patients with MVD and 23% to 28% reductions in risk in patients without MVD., Conclusions: Evolocumab reduced the rate of major adverse cardiovascular event in patients with and without MVD. The benefit tended to occur earlier and was larger in patients with MVD. However, the magnitude grew over time in both groups. These data support early initiation of intensive low-density lipoprotein cholesterol lowering both in patients with and without MVD., Competing Interests: Funding Support and Author Disclosures FOURIER and FOURIER-OLE were funded by Amgen. Dr O’Donoghue has received grant funding through Brigham and Women’s Hospital from Amgen, Novartis, AstraZeneca, Janssen, Intarcia, and GlaxoSmithKline; and has received consulting fees from Amgen, Novartis, AstraZeneca, and Janssen. Dr De Ferrari has received research support through his institution from Livanova, Merck, and Novartis; has received a steering committee fee from Amgen; and has received consulting and speaker fees from Amgen, AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, and Novartis. Ms Ran and Dr Im are employees of the TIMI Study Group, which has received research grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, Inc, ARCA Biopharma, AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Ionis, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Roche, Saghmos Therapeutics, Siemens Healthcare Diagnostics, Softcell Medical Limited, Verve Therapeutics, and Zora Biosciences. Dr López, Ms Elliott-Davey, Dr Wang, and Dr Monsalvo are employed by and own stock in Amgen. Dr Atar has received speaker and consultancy honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Philips, Roche-Diagnostics, Sanofi, Takeda, and Vifor Pharma; and has received research grant support (to the institution) from Bristol Myers Squibb/Pfizer, Medtronic, Bayer, and Roche Diagnostics. Dr Keech has received grants and personal fees from Abbott and Mylan; and has received personal fees from Amgen, AstraZeneca, Pfizer, Sanofi, and Novartis. Dr Giugliano has received research grant support through Brigham and Women’s Hospital from Amgen, Daiichi-Sankyo, and Ionis; has received speaker honoraria from Amgen, Daiichi-Sankyo, Dr Reddy’s Laboratories, Medical Education Resources, and SUMMEET; and has received consulting fees from Daiichi-Sankyo, Inventiva, and Sanofi. Dr Sabatine has received research grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, Inc, AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Ionis, Merck, Novartis, Pfizer, Saghmos Therapeutics, and Verve Therapeutics; and has received consulting fees from Amgen, Beren Therapeutics, Boehringer Ingelheim, Dr Reddy’s Laboratories, Merck, Novo Nordisk, and Precision BioSciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The cardiac autonomic nervous system (CANS) plays a pivotal role in cardiac homeostasis as well as in cardiac pathology. The first level of cardiac autonomic control, the intrinsic cardiac nervous system (ICNS), is located within the epicardial fat pads and is physically organized in ganglionated plexi (GPs). The ICNS system does not only contain parasympathetic cardiac efferent neurons, as long believed, but also afferent neurons and local circuit neurons. Thanks to its high degree of connectivity, combined with neuronal plasticity and memory capacity, the ICNS allows for a beat-to-beat control of all cardiac functions and responses as well as integration with extracardiac and higher centers for longer-term cardiovascular reflexes. The present review provides a detailed overview of the current knowledge of the bidirectional connection between the ICNS and the most studied cardiac pathologies/conditions (myocardial infarction, heart failure, arrhythmias and heart transplant) and the potential therapeutic implications. Indeed, GP modulation with efferent activity inhibition, differently achieved, has been studied for atrial fibrillation and functional bradyarrhythmias, while GP modulation with efferent activity stimulation has been evaluated for myocardial infarction, heart failure and ventricular arrhythmias. Electrical therapy has the unique potential to allow for both kinds of ICNS modulation while preserving the anatomical integrity of the system.

Objectives: To evaluate the diagnostic performance of a short non-contrast CMR (ShtCMR) protocol relative to a matched standard comprehensive CMR (StdCMR) protocol in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA)., Methods: This multicenter retrospective study included patients with a working diagnosis of MINOCA who underwent a StdCMR between January 2019 and December 2020. An expert and a non-expert reader performed a blinded reading with the ShtCMR (long-axis cine images, T2w-STIR, T1- and T2-mapping). A consensus reading of the StdCMR (reference standard) was performed at least 3 months after the ShtCMR reading session. Readers were asked to report the following: (1) diagnosis; (2) level of confidence in their diagnosis with the ShtCMR; (3) number of myocardial segments involved, and (4) functional parameters., Results: A total of 179 patients were enrolled. The ShtCMR lasted 21 ± 9 min and the StdCMR 45 ± 11 min (p < 0.0001). ShtCMR allowed reaching the same diagnosis as StdCMR in 85% of patients when interpreted by expert readers (rising from 66% for poor confidence to 99% for good, p = 0.0001) and in 73% (p = 0.01) by non-expert ones (60% for poor vs 89% for good confidence, p = 0.0001). Overall, the ShtCMR overestimated the ejection fraction, underestimated cardiac volumes (p < 0.01), and underestimated the number of segments involved by pathology (p = 0.0008) when compared with the StdCMR., Conclusion: The ShtCMR was found to be a debatable alternative to the StdCMR in patients with MINOCA. Nevertheless, when an experienced reader reaches a good or very good diagnostic confidence using the ShtCMR, the reader may choose to stop the examination, reducing the length of the CMR without affecting the patient's diagnosis., Clinical Relevance Statement: A short non-contrast CMR protocol may be a viable alternative to standard protocols in selected CMR studies of patients with MINOCA, allowing for faster diagnosis while reducing time and resources and increasing the number of patients who can be scanned., Key Points: • The ShtCMR lasted 21 ± 9 min and the StdCMR 45 ± 11 min (p < 0.0001). • In 57% of patients with MINOCA, the experienced reader considers that contrast medium is probably not necessary for diagnosis without affecting the patient's diagnosis (99% of agreement rate between ShtCMR and StdCMR)., (© 2023. The Author(s).)