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

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

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

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

Aims The aims of this study is to assess by an updated meta-analysis the clinical outcomes related to permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) at long-term (≥12 months) follow-up (LTF). Methods and results A comprehensive literature research was performed on PubMed and EMBASE. The primary endpoint was all-cause death. Secondary endpoints were rehospitalization for heart failure, stroke, and myocardial infarction. A subgroup analysis was performed according to the Society of Thoracic Surgeon—Predicted Risk of Mortality (STS-PROM) score. This study is registered with PROSPERO (CRD42021243301). A total of 51 069 patients undergoing TAVI from 31 observational studies were included. The mean duration of follow-up was 22 months. At LTF, PPI post-TAVI was associated with a higher risk of all-cause death [risk ratio (RR) 1.18, 95% confidence interval (CI) 1.10–1.25; P < 0.001] and rehospitalization for heart failure (RR 1.32, 95% CI 1.13–1.52; P < 0.001). In contrast, the risks of stroke and myocardial infarction were not affected. Among the 20 studies that reported procedural risk, the association between PPI and all-cause death risk at LTF was statistically significant only in studies enrolling patients with high STS-PROM score (RR 1.25, 95% CI 1.12–1.40), although there was a similar tendency of the results in those at medium and low risk. Conclusion Patients necessitating PPI after TAVI have a higher long-term risk of all-cause death and rehospitalization for heart failure as compared to those who do not receive PPI.

Pre-clinical congestion markers of worsening heart failure (HF) can be monitored by devices and may support the management of patients with HF. We aimed to assess whether congestion-guided HF management according to device-based remote monitoring strategies is more effective than standard therapy.A comprehensive literature research for randomized controlled trials (RCTs) comparing device-based remote monitoring strategies for congestion-guided HF management versus standard therapy was performed on PubMed, Embase, and CENTRAL databases. Incidence rate ratios (IRRs) and associated 95% confidence intervals (CIs) were calculated using the Poisson regression model with random study effects. The primary outcome was a composite of all-cause death and HF hospitalizations. Secondary endpoints included the individual components of the primary outcome. A total of 4347 patients from eight RCTs were included. Findings varied according to the type of parameters monitored. Compared with standard therapy, haemodynamic-guided strategy (4 trials, 2224 patients, 12-month follow-up) reduced the risk of the primary composite outcome (IRR 0.79, 95% CI 0.70-0.89) and HF hospitalizations (IRR 0.76, 95% CI 0.67-0.86), without a significant impact on all-cause death (IRR 0.93, 95% CI 0.72-1.21). In contrast, impedance-guided strategy (4 trials, 2123 patients, 19-month follow-up) did not provide significant benefits.Haemodynamic-guided HF management is associated with better clinical outcomes as compared to standard clinical care.

Aims As compared with surgery, transcatheter aortic valve implantation (TAVI) is associated with increased need for permanent pacemaker implantation (PPMI). The clinical impact of PPMI post-TAVI has not been fully established. To assess by an updated meta-analysis the clinical outcomes related to PPMI after TAVI at long-term (≥12 months) follow-up (LTF). Methods and results A comprehensive literature research was performed on PubMed and EMBASE. The primary endpoint was all-cause death. Secondary endpoints were rehospitalization for heart failure, stroke, and myocardial infarction. A subgroup analysis was performed according to Society of Thoracic Surgeon—Predicted Risk of Mortality (STS-PROM) score. A total of 31 studies were identified, providing data on 51 069 patients. The mean duration of follow-up was 22 months. At LTF, PPMI post-TAVI was associated with a higher risk of all-cause death [22.9% vs. 19.6%; risk ratio (RR), 1.18, 95% confidence interval (CI), 1.10–1.25; P Conclusions Patients necessitating PPMI after TAVI have higher long-term risk of all-cause death and rehospitalization for heart failure as compared to those who do not receive PPMI. Thus, strategies aimed at reducing need for PPMI might improve survival after TAVI.

Methods and results Platypnea–Orthodeoxia syndrome (POS) is an uncommon but challenging clinical condition characterized by positional dyspnoea (platypnea) and arterial desaturation (orthodeoxia) in the upright position that improve in the supine position. POS can occur insidiously, as progressive unexplained oxygen desaturation for months or years, or as acute life-threatening unexplained hypoxaemia. The most common cause is the presence of an intracardiac shunt (patent foramen ovale and other interatrial defects) associated with a secondary anatomic or functional defect that serve as substrate for a right to left intracardiac shunt leading to oxygen desaturation. Conclusions Herein we present the case of a nonagenarian with a known history of ascending aortic aneurysm, that was admitted to the emergency department of our institution with a complaint of intermittent chest pain and dyspnoea. POS was then diagnosed, and the patient underwent a successful percutaneous closure with an Amplatzer™ device (25/25 mm) with minimal residual right-to-left shunt leading to a significant relief of the dyspnoea and improvement of arterial saturation. We also herein revise the clinical presentation, pathophysiology, diagnostic work-up, and management of patients with POS, aiming at increasing the awareness of this uncommon but often misdiagnosed treatable condition.

Inflammation is the main pathophysiological process involved in atherosclerotic plaque formation, progression, instability, and healing during the evolution of coronary artery disease (CAD). The use of colchicine, a drug used for decades in non-ischemic cardiovascular (CV) diseases and/or systemic inflammatory conditions, stimulated new perspectives on its potential application in patients with CAD. Previous mechanistic and preclinical studies revealed anti-inflammatory and immunomodulatory effects of colchicine exerted through its principal mechanism of microtubule polymerization inhibition, however, other pleiotropic effects beneficial to the CV system were observed such as inhibition of platelet aggregation and suppression of endothelial proliferation. In randomized double-blinded clinical trials informing our clinical practice, low doses of colchicine were associated with the significant reduction of cardiovascular events in patients with stable CAD and chronic coronary syndrome (CCS) while in patients with a recent acute coronary syndrome (ACS), early initiation of colchicine treatment significantly reduced major adverse CV events (MACE). On the other hand, the safety profile of colchicine and its potential causal relationship to the observed increase in non-CV deaths warrants further investigation. For these reasons, postulates of precision medicine and patient-tailored approach with regards to benefits and harms of colchicine treatment should be employed at all times due to potential toxicity of colchicine as well as the currently unresolved signal of harm concerning non-CV mortality. The main goal of this review is to provide a balanced, critical, and comprehensive evaluation of currently available evidence with respect to colchicine use in the setting of CAD.

Platypnoea-orthodeoxia syndrome (POS) is an uncommon but challenging clinical condition characterised by positional dyspnoea (platypnoea) and arterial desaturation (orthodeoxia) in the upright position that improve in the supine position. Since its first description, many cases have been reported and many conditions have been associated with this syndrome. Herein, we review the clinical presentation, pathophysiology, diagnostic work-up and management of patients with POS, aiming to increase the awareness of this often misdiagnosed condition.

Kinematics and flexibility properties of both natural and replaced ankle joints are affected by the geometry of the articulating surfaces. Recent studies proposed an original saddle-shaped, skewed, truncated cone with laterally oriented apex, as tibiotalar contact surfaces for ankle prosthesis. The goal of this study was to compare in vitro this novel design with traditional cylindrical or medially centered conic geometries in terms of their ability to replicate the natural ankle joint mechanics. Ten lower limb cadaver specimens underwent a validated process of custom design for the replacement of the natural ankle joint. The process included medical imaging, 3D modeling and printing of implantable sets of artificial articular surfaces based on these three geometries. Kinematics and flexibility of the overall ankle complex, along with the separate ankle and subtalar joints, were measured under cyclic loading. In the neutral and in maximum plantarflexion positions, the range of motion under torques in the three anatomical planes of the three custom artificial surfaces was not significantly different from that of the natural surfaces. In maximum dorsiflexion the difference was significant for all three artificial surfaces at the ankle complex, and only for the cylindrical and medially centered conic geometries at the tibiotalar joint. Natural joint flexibility was restored by the artificial surfaces nearly in all positions. The present study provides experimental support for designing articular surfaces matching the specific morphology of the ankle to be replace, and lays the foundations of the overall process for designing and manufacturing patient-specific total ankle replacements.

Composting represents a valuable strategy for recycling orange processing waste for use as soil conditioner, provided compost maturity is duly evaluated. Following a 5-month aerobic bioconversion, orange waste reached an acceptable degree of maturity in terms of humification parameters, absence of phytotoxicity (determined on test plants according to ISO methods) and low content of simple phenolic compounds. A greenhouse experiment with two nursery crops (tomato and zucchini) showed that, depending on the characteristics of the growing substrate (vermiculite or perlite), orange compost addition selectively induced pH and electrical conductivity (EC) increases, which in turn would affect plant growth responses. In field crops shoot mass weight was increased after compost addition. Results suggest that at field scale, orange compost may be used for organic fertilization; while in nursery crops it can be mixed with commercial potting substrates selected in relation to plant sensitivity. In horticultural crop...