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

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

Background 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 Heart failure with preserved ejection fraction (HFpEF) represents nowadays the most frequent presentation of heart failure (HF) in patients aged > 65 years. The underlying reason for the failure of the vast majority of randomized controlled trials (RCTs) in HFpEF patients has been identified in the heterogeneity of pathophysiology and clinical phenotype of this clinical syndrome. Coronary microvascular dysfunction (CMD) represents one among various pathophysiological mechanisms, together with pulmonary vascular disease, pericardial restraint, impaired chronotropic reserve and abnormal autonomic tone. Whether CMD-HFpEF endotype differs from the others in terms of echocardiographic parameters and clinical outcomes is still a matter of debate. Therefore, a systematic review and meta-analysis were performed in order to compare HFpEF populations with or without CMD in terms of echocardiographic features and clinical outcomes. Methods We searched for articles published in PubMed, Scopus and Wiley comparing HFpEF population with or without CMD up to 1st September 2022. Observational studies, reporting echocardiographic parameters mentioned in HFA-PEFF score and/or clinical time to event data, were included. E/e’ ratio, left atrial volume index (LAVi) and left ventricular mass index (LVMi) constituted our three parameters of choice and Hedge's g was the summary effect size. The composite of HF hospitalization and all-cause death represented our clinical endpoint. Meta-regressions according to follow-up time were performed in order to explore potential heterogeneity sources across studies. Results We identified 9 prospective observational studies, enrolling 797 patients with HFpEF. On pooled analysis, patients with CMD present a more severe echocardiographic phenotype, determined by a higher LAVi [effect size (ES) 0.40; Confidence Interval (CI) 0.11, 1.69], E/e’ ratio (ES 0.65; CI 0.28, 1.02) and LVMi (ES 0.27; CI 0.01, 0.53) compared to no-CMD patients. Furthermore, CMD patients showed a significant higher rate of the composite endpoint of all-cause-death and hospitalization for HF (HR 3.22, CI 1.2-8.5, p 0.02). At meta-regression, a significant correlation was found between logarithmic hazard ratios and follow-up time reported (z=2.03, p value 0.04), suggesting that long-term follow-up of CMD-HFpEF patients is required to track the natural trajectory of the disease. Conclusions Aside from being considered a pathophysiological hallmark in the development of HFpEF, CMD seems to play an aggravating role in the progression of the disease, leading both to more severe echocardiographic parameters and worse clinical outcomes compared to other endotypes. Thus, different echocardiographic thresholds could allow for a better prognostic stratification and for identifying the subset of patients who deserve a CMD assessment and who are eventually more likely to benefit from drugs targeting CMD.

Background Current guidelines recommend that patients with heart failure and a reduced ejection fraction (HFrEF) should receive four foundational treatments, i.e. renin-angiotensin system inhibitor (RASi) or angiotensin-receptor neprilysin inhibitor (ARNi), β-blocker, mineralocorticoid receptor antagonist (MRA) and sodium-glucose cotransporter 2 inhibitor (SGLT2i). There is emerging consensus that simultaneous initiation or rapid sequencing provide greater benefit, enhancing tolerability of these therapies and improving outcomes. However, implementation of a comprehensive approach is limited by common underuse and underdosing, and paucity of data exists on initiating the four pharmacological pillars of HFrEF during hospitalization or at discharge. Aim To investigate the feasibility of a comprehensive pharmacological approach in patients with HFrEF at discharge after an episode of heart failure (HF) hospitalization in a tertiary referral center. Methods In-patients with HFrEF and a first HF hospitalization (2019-2021) were categorized according to the number/type of treatments prescribed at discharge. Prevalence of contraindications and cautions for HFrEF treatments – as defined by current European Society of Cardiology (ESC) guidelines on HF – was as assessed. Logistic regression models were fitted to assess predictors of number of treatments prescribed and risk of re-hospitalization. Results Among 305 patients with HFrEF, 49.2% received at least two current recommended drugs. A β-blocker was prescribed in 93.4% of patients, and a RASi/ARNi in 68.2%. Based on current recommendations, 46.2% of patients could receive four foundational drugs. An MRA was prescribed in 32.5% of patients and 100% of patients did not show contraindications to MRA use. Renal dysfunction was present in 13.1% of patients, while hypotension in 11.8%. Bradycardia and renal dysfunction were associated with lower number of drugs prescribed [adjusted OR (95% CI) 0.18 (0.06-0.50), and 0.50 (0.39-0.64), respectively]. A higher number of drugs used was associated with no rehospitalization during the 30 days after discharge [OR (95% CI) 0.22 (0.10-0.49) per number of pillars increase]. Conclusions Based on the presence/absence of contraindications, a quadruple therapy could be implementable in a contemporary cohort of HFrEF in-patients at discharge. Renal dysfunction and bradycardia were the main prevalent conditions limiting the achievement of a more comprehensive therapeutic approach. Use of a higher number of drugs was associated with lower risk of re-hospitalization within 30 days after discharge.

Takotsubo syndrome (TTS) is a rare cardiac disease, characterized by transient regional wall motion abnormalities without evidence of obstructive coronary artery stenoses, mainly triggered by emotion or physical stressors. Reverse Takotsubo syndrome (rTTS), an atypical variant with basal segments involvement, is frequently associated with neurological disorders, including patients with amyotrophic lateral sclerosis (ALS). We reported the case of a 54 years old woman who experienced two consecutive episodes of TTS with different wall motion patterns, complicated by a recurrent episode and arrhythmic events. A Caucasian woman, affected by ALS, was hospitalized in our department due to anemia and recurrent episodes of hematochezia. Following a week of relative clinical stability, the patient experienced acute deterioration with generalized malaise and worsening dyspnea. CT scan excluded pulmonary causes, whereas EKG (ST segment depression in the lower and lateral leads), blood test (increase in high-sensitive cardiac troponins) and TTE (severe impairment of LVEF, with akinesia of basal segments) revealed a cardiac etiology. Coronary angiography and left ventriculography were performed, documenting a wall motion pattern consistent with rTTS. After an initial management in intensive care unit, clinical stability was obtained with a complete recovery of left ventricular systolic function. The patient was discharged but one month later, due to bacterial pneumonia, she was readmitted in our ward and antibiotic therapy was started. Two days later an acute deterioration of clinical status occurred, characterized by dyspnea, altered state of consciousness and marked hypotension. TTE revealed a severe left ventricular systolic dysfunction with apical akinesia and preserved contractility of basal segments, so a diagnosis of typical TTS was made. Three weeks later the clinical scenario became more complicated due to advanced atrioventricular block, with phases of atrioventricular dissociation and ventricular escape-rhythm. Therefore, in light of the increased risk of infectious complications, she underwent implantation of a leadless pacemaker (PMK). This clinical case represents the first report of recurrent episodes of TTS, one of which as rTTS, in a patient affected by ALS. It is worth noting that the first episode of TTS had atypical clinical presentation (dyspnea without chest pain), the EKG showed diffuse ST-segment depression (totally different from classical TTS typical electrocardiographic alterations), and TTE confirmed a different phenotype of segment involvement (unsurprisingly InterTAK Diagnostic Score was low). TTS recurrence is an extremely rare event, even if in this case there were two well defined triggers such as anemia and pneumonia. On the other hand it is reasonable to think that non-use of BBs after the first episode may have contributed to the occurrence of the next event, affecting different segments compared to the previous episode. Furthermore, advanced atrioventricular (AV) block represents a rare complication of TTS, most probably due to catecholamine stress or increased vagal tone, often requiring PMK implantation. In conclusion TTS represents an important frequent cardiac complication in patients affected by ALS, often still underdiagnosed. Therefore clinicians must keep their guard up with TTS, especially in the cases with atypical clinical presentation.

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 Randomized trials support the safety and efficacy of direct oral anticoagulants (DOACs) vs. vitamin K antagonists (VKA) in patients with nonvalvular atrial fibrillation (AF), leading to increased use of these compounds. Crushed forms of DOACs have shown to be reliable, but evidence supporting percutaneous endoscopic gastrostomy (PEG) delivery is lacking. PEG is a long-term option for enteral food and drug delivery in patients unable to maintain oral intake, bypassing the risks and disadvantages of parenteral nutrition. We investigate the safety and efficacy of Edoxaban administered via PEG in patients with atrial fibrillation and a clinical indication for a long-term anticoagulation. Methods and results In this prospective, single centre observational study, 12 PEG-treated patients with indication to anticoagulation will receive edoxaban via PEG and will be followed-up to 6 months. Plasma anti-Factor Xa activity and edoxaban concentrations will be assessed. Thromboembolic (ischaemic stroke, systemic embolism, venous thromboembolism) and bleeding events (Bleeding Academic Research Consortium and Thrombolysis in Myocardial Infarction) will be recorded at 1 and 6 months. A retrospective analysis of 5 AF cases undergoing PEG-implantation at our Institution, who received edoxaban via PEG, showed plasma anti-FXa levels at steady state of 146 ± 15 ng/ml, without major adverse event at a mean follow-up of 6 months. Conclusion We prospectively investigate PEG-administration of edoxaban in PEG-treated patients requiring long term anticoagulation. Our preliminary retrospective data support this route of DOAC administration.

Background Cardiac amyloidosis (CA) is a rapidly progressive infiltrative cardiomyopathy, whose role is emerging as a not-so-rare disorder leading to heart failure (HF). Myocardial bridge (MB) is the most common inborn coronary artery variant, and its clinical relevance is still matter of debate. The exceptional coexistence of these two conditions could accelerate disease progression and worsen the already compromised clinical conditions. Case summary We present the case of a 76-year-old female patient experiencing relapsing HF decompensation and presenting to our centre with dyspnoea at rest and severe peripheral congestion. Echocardiogram showed severe concentric hypertrophy, severe biventricular contractile dysfunction, and third-degree diastolic dysfunction. Coronary angiography excluded epicardial atherosclerotic disease, though displaying a long intramyocardial course of left anterior descending artery. Physiological invasive test was achieved in terms of instantaneous wave-free ratio (iFR), both at baseline and after inotropic and chronotropic stimuli, and attested haemodynamic significance. Concurrently, the diagnostic flow chart for CA was accomplished, by means of both invasive (periumbilical fat biopsy, bone marrow aspiration) and non-invasive tests (99mTc-diphosphonate scintigraphy, serum-urine immunofixation) that confirmed the suspect of primary amyloidosis. Acute HF therapy was personalized according to the singularity of the case, avoiding both nitrates and beta-blockers, then first cycle of chemotherapy was started. Discussion Our clinical case shows a unique interaction between infiltrative cardiomyopathy and coronary artery abnormality. Amyloidosis can contribute to the ischaemic burden of the MB and this may, in turn, abbreviate the path to HF decompensation.

Extensive data support the superior safety without any trade-off in efficacy of direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKA) in patients with nonvalvular atrial fibrillation, deep venous thrombosis or pulmonary embolism. Whether DOACs may be successfully used to treat complex and fragile patients with percutaneous endoscopic gastrostomy (PEG) remains to be proven. The purpose of this pilot study was to evaluate the feasibility, anticoagulant effect, and preliminary safety/efficacy profile of edoxaban administered via PEG in patients with an indication for long-term oral anticoagulation.In this prospective, single-arm, pilot study, 12 patients with PEG and guideline-recommended indication for anticoagulation for nonvalvular atrial fibrillation were prospectively enrolled. Crushed edoxaban at approved doses was administered via PEG. Quantitative measures of edoxaban's anti-factor Xa activity were performed at steady state. Thromboembolic and bleeding events were assessed at one-month follow-up.Steady state edoxaban plasma levels were at therapeutic range in all patients; mean plasma concentration was 208.5 (±78.6) ng/ml. At one month follow-up, none had suffered a thromboembolic event; one developed minor bleeding, and one died from non-cardiovascular death, owing to sudden worsening of a pre-existing underlying severe condition.In this pilot investigation, we report for the first time that crushed edoxaban, administered at approved doses through PEG in fragile and complex patients, is feasible, results in therapeutic edoxaban concentrations, and is apparently effective and safe.

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.

Electronic cigarettes use is a growing trend in contemporary societies, with the propensity to compete with traditional tobacco smoking. Some preclinical studies demonstrated the toxic and detrimental effects of electronic cigarettes liquid components. Its impact on human health remains unknown and insufficiently studied. While some studies suggest that electronic cigarettes use might be associated with endothelial dysfunction, impaired platelet function and increased risk of adverse clinical events, other studies did not confirm these findings and epidemiological data mostly suggest that the use of electronic cigarettes appears to be safer than that of traditional tobacco cigarettes. This article provides an up-to-date overview of the current state of knowledge regarding electronic cigarettes and their impact on human health, with special emphasis on their effect on cardiovascular diseases.

Aims Myocardial bridge (MB) is the most common inborn coronary artery variant in which a segment of an epicardial coronary artery takes a tunneled course under a bridge of myocardium. MB has been documented from 1.5% to 16% of invasive angiographic series thus the true prevalence of MB is uncertain. The clinical relevance of MB is heterogeneous, being usually an asymptomatic bystander. However, a growing body of evidence suggests its association with myocardial ischaemia. In the present work, by setting up a database of patients affected by MB, we sought to assess their clinical characteristics and risk of major adverse cardiac events (MACE). Methods and results This is a prospective/retrospective study and observational study in which we included 17 681 patients referred to undergo invasive coronary angiography (ICA) for suspected coronary artery disease. During the screening phase, we found that 338 cases (26 non-recruitable) were reported to have MB (1.9%). In-hospital clinical-instrumental data was acquired after ICA. The data obtained in the follow-up (FUP) visit is also included in the study. In particular, we recorded MACE and Seattle Angina Questionnaire (SAQ). The most frequent location of MB was the LAD coronary artery (96.8%). Other locations were the circumflex artery (1.3%), the right coronary artery (1%), the posterior interventricular artery (0.6%), and the first diagonal artery (0.3%). Chronic coronary syndrome (CCS) was the most frequent clinical presentation (47.5%). A big proportion (34.6%) of our patients were found to have MB during the occurrence of an acute coronary syndrome (ACS). In acute setting, unstable angina was the most frequent clinical presentation (17.6%). 47 patients (15%) underwent coronary angiography with provocative test (intracoronary acetylcholine) in order to search vasomotor disorders: according to COVADIS criteria, 17 procedures (5.5%) resulted positive for vasospastic angina (VSA). Invasive functional assessment with FFR/iFR was accomplished to assess the haemodynamic significance both of MBs and atherosclerotic plaques proximal to the MB segment in 35 patients (11.2%): in nine procedures (2.9%), functional tests resulted positive. β-Blockers (BBs) are suggested as first-line drugs as they increase diastolic filling time, by decreasing heart rate. Calcium channel blockers (CCBs) are useful, in VSA setting, to reduce epicardial spasm. In our court, 40% of patients toke BBs and 20% of patients toke CCBs at admission. The primary endpoint of the study is the incidence of MACE, defined as the composite of cardiac death, myocardial infarction and cardiac hospitalization. Considering patients who have already undergone FUP (114; 36.5%), we recorded 19 MACE (16.7% of patients with FUP). The secondary endpoint is the rate of patients with SAQ Angina Summary Score < 70: the rate of patients with SAQ < 70 is 23.7% at 6 months, 23.8% at 12 months and 23.2% at 24 months. Conclusions MB has been typically considered benign and asymptomatic, but its clinical relevance is still matter of debate. A remarkable proportion of our patients were found to have a MB during the occurrence of ACS or CCS, highlighting that different mechanisms of ischaemia may coexist. Furthermore, invasive functional assessment shows a plausible correlation between MB and vasomotor disorders. Our study is still ongoing, and we hope to maximize the data in order to have a solid comprehension of MB and to propose the assessment that may indicate a tailored therapy.

Aims Over the last decades, both the improvement in cardiovascular prevention programmes and the advancement in medical and invasive therapies facing ischaemic heart disease have granted an outstanding reduction in mortality rates. However, coronary heart disease remains, by far, the most common disease in developed countries, and the progressive ageing of population leads to a constantly increasing prevalence of chronic coronary syndrome (CCS). The consequence is an unsustainable demand for access to collapsing hospital clinic and doctor’s office. The dramatic Covid-19 era has become the testing ground for alternative ways to deliver healthcare avoiding in-hospital contacts, thus affirming the validity of telemedicine as a key tool to improve the patient journey. In our centre, video consults have been integrated to CCS patients’ clinical care pathway, not only preventing the risk of contagion but also laying the groundwork for a paradigm shift in clinical care course. Methods and results Since pandemic outbreak, Lazio Region offered to its inhabitants free of charge teleconsulting for both primary care and specialist referral. At the cardiovascular department of Fondazione Policlinico Gemelli IRCCS, this opportunity has been recently applied to optimize the chronic coronary syndrome patient journey. Specifically, videoconsulting has been used in different steps of CCS clinical course, replacing both in-person first visit and follow-up consultation after percutaneous myocardial revascularization. Being CCS a context in which the therapy optimization or the transition to higher level tests are mainly indicated by symptoms, these remote consultations could work as well as in-hospital visits to assess risk stratification and to consequently arrange the best therapeutic–diagnostic pathway. Besides, as COVID-19 pandemic caused significant delays, further remote visits have addressed the need to keep in contact with patients waiting for coronary angiography and to reassess their urgency criteria. In our department, over last 9 months, 141 patients have been examined and followed-up through teleconsulting, amounting to 34.1% of all supplied visits. Despite a high median age (67 ± 19.7 years), the drop-out rate of the contacted patients due to inability or denial was quite low (7.5%) and this high adherence to videoconsulting suggests time is ripe for a full telemedicine employment in clinical care course. In the cohort of patients waiting for coronary angiography, a telemedical reassessment led to a significant rate of priority class switch (42.7%), probably preventing adverse cardiac events in those individuals with worsening symptoms (systematically evaluated using Seattle Angina Questionnaire). Of note, the implementation of this parallel virtual pathway for these patients allowed us to decrease the waiting times for in-person visits at our CCS clinic, with an estimated time reduction of almost 3 months. This result supports our idea that the adoption of a remote pathway for chronic illness management, like CCS, may provide more opportunities for treatment of severe cases at in-person clinics that are often overcrowded. Conclusions In conclusion, all the potential of telehealth to empower primary and specialty health care is gradually emerging, and CCS seems the perfect setting for an integrated physical and virtual health system.

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.

Background Myocardial bridge (MB) is the most common inborn coronary artery variant, in which a portion of myocardium overlies a major epicardial coronary artery segment. Myocardial bridge has been for long considered a benign condition, although it has been shown to cause effort-related ischaemia. Case summary We present the case of a 17-year-old female patient experiencing chest pain during physical activity. Since her symptoms became unbearable, electrocardiogram and echocardiography were performed together with a coronary computed tomography scan, revealing an MB on proximal-mid left anterior descending artery. In order to unequivocally unmask the ischaemic burden lent by MB, the patient underwent coronary angiography and physiological invasive test: instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) were calculated, both at baseline and after dobutamine infusion (5 µg/kg/min). At baseline, iFR value was borderline (= 0.89), whereas after dobutamine infusion and increase in the heart rate, the patient suffered chest pain. This symptom was associated with a decrease in the iFR value up to 0.77. Consistently, when FFR was performed, a value of 0.92 was observed at baseline, while after inotrope infusion the FFR reached the haemodynamic significance (= 0.79). Therefore, a medical treatment with bisoprolol was started. Discussion Our clinical case shows the importance of a comprehensive non-invasive and invasive assessment of MB in young patients experiencing chest pain, with significant limitation in the daily life. The coronary functional indexes allow to detect the presence of MB-derived ischaemia, thus guiding the decision to undertake a medical/surgical therapy.

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

Background Ticagrelor is a reversibly binding, direct-acting, oral, P2Y12 antagonist used for the prevention of atherothrombotic events in patients with coronary artery disease (CAD). Ticagrelor blocks adenosine reuptake through the inhibition of equilibrative nucleoside transporter 1 (ENT-1) on erythrocytes and platelets, thereby facilitating adenosine-induced physiological responses such as an increase in coronary blood flow velocity. Meanwhile, adenosine plays an important role in triggering ischemic preconditioning through the activation of the A1 receptor. Therefore, an increase in ticagrelor-enhanced adenosine bioavailability may confer beneficial effects through mechanisms related to preconditioning activation and improvement of coronary microvascular dysfunction. Methods To determine whether ticagrelor can trigger ischemic preconditioning and influence microvascular function, we designed this prospective, open-label, pilot study that enrolled patients with stable multivessel CAD requiring staged, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI). Participants will be randomized in 1:1 ratios either to ticagrelor (loading dose (LD) 180 mg, maintenance dose (MD) 90 mg bid) or to clopidogrel (LD 600 mg, MD 75 mg) from 3 to 1 days before the scheduled PCI. The PCI operators will be blinded to the randomization arm. The primary endpoint is the delta (difference) between ST segment elevations (in millimeters, mm) as assessed by intracoronary electrocardiogram (ECG) during the two-step sequential coronary balloon inflation in the culprit vessel. Secondary endpoints are 1) changes in coronary flow reserve (CFR), index of microvascular resistance (IMR), and FFR measured in the culprit vessel and reference vessel at the end of PCI, and 2) angina score during inflations. This study started in 2018 with the aim of enrolling 100 patients. Based on the rate of negative FFR up to 30% and a drop-out rate up to 10%, we expect to detect an absolute difference of 4 mm among the study arms in the mean change of ST elevation following repeated balloon inflations. All study procedures were reviewed and approved by the Ethical Committee of the Catholic University of Sacred Heart. Discussion Ticagrelor might improve ischemia tolerance and microvascular function compared to clopidogrel, and these effects might translate to better long-term clinical outcomes. Trial registration EudraCT No. 2016–004746-28. No. NCT02701140. Trial status Information provided in this manuscript refers to the definitive version (n. 3.0) of the study protocol, dated 31 October 2017, and includes all protocol amendments. Recruitment started on 18 September 2018 and is currently ongoing. The enrollment is expected to be completed by the end of 2019. Trial sponsor Fondazione Policlinico Universitario A. Gemelli – Roma, Polo di Scienze Cardiovascolari e Toraciche, Largo Agostino Gemelli 8, 00168 Rome, Italy.

Aims The ORal anticoagulants In fraGile patients with percutAneous endoscopic gastrostoMy and atrIal fibrillation (ORIGAMI) study investigates the safety and efficacy of Edoxaban administered via PEG in patients with atrial fibrillation and a clinical indication for a long-term anticoagulation. Design In this prospective, single-centre observational study, 12 PEG-treated patients with indication to anticoagulation will receive edoxaban via PEG and will be followed up to 6 months. Plasma antifactor Xa activity and edoxaban concentrations will be assessed. Thromboembolic (ischaemic stroke, systemic embolism, venous thromboembolism) and bleeding events (Bleeding Academic Research Consortium and Thrombolysis in Myocardial Infarction) will be recorded at 1 and 6 months. Preliminary results A retrospective analysis of five atrial fibrillation cases undergoing PEG implantation at our Institution who received edoxaban via PEG showed plasma anti-FXa levels at a steady state of 146 ± 15 ng/ml, without major adverse event at a mean follow-up of 6 months. Conclusion ORIGAMI prospectively investigates PEG-administration of edoxaban in PEG-treated patients requiring long-term anticoagulation. Our preliminary retrospective data support this route of DOAC administration. Clinicaltrialsgov identifier NCT04271293.

Background: the RIGENERA trial assessed the efficacy of granulocyte-colony stimulating factor (G-CSF) in the improvement of clinical outcomes in patients with severe acute myocardial infarction. However, there is no evidence available regarding the long-term safety and efficacy of this treatment. Methods: in order to evaluate the long-term effects on the incidence of major adverse events, on the symptom burden, on the quality of life and the mean life expectancy and on the left ventricular (LV) function, we performed a clinical and echocardiographic evaluation together with an assessment using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the Seattle Heart Failure Model (SHFM) at 10-years follow-up, in the patients cohorts enrolled in the RIGENERA trial. Results: thirty-two patients were eligible for the prospective clinical and echocardiography analyses. A significant reduction in adverse LV remodeling was observed in G-CSF group compared to controls, 9% vs. 48% (p = 0.030). The New York Heart Association (NYHA) functional class was lower in G-CSF group vs. controls (p = 0.040), with lower burden of symptoms and higher quality of life (p = 0.049). The mean life expectancy was significantly higher in G-CSF group compared to controls (15 &plusmn, 4 years vs. 12 &plusmn, 4 years, p = 0.046. No difference was found in the incidence of major adverse events. Conclusions: this longest available follow-up on G-CSF treatment in patients with severe acute myocardial infarction (AMI) showed that this treatment was safe and associated with a reduction of adverse LV remodeling and higher quality of life, in comparison with standard-of-care treatment.

New technologies have been recently introduced to improve the monitoring of patients with chronic syndromes such as heart failure. Devices can now be employed to gather large amounts of data and data processing through artificial intelligence techniques may improve heart failure management and reduce costs. The analysis of large datasets using an artificial intelligence technique is leading to a paradigm shift in the era of precision medicine. However, the assessment of clinical safety and the evaluation of the potential benefits is still a matter of debate. In this article, the authors aim to focus on the development of these new tools and to draw the attention to their transition in daily clinical practice.

Heart failure with preserved ejection fraction (HFpEF) is an increasingly studied entity accounting for 50% of all diagnosed heart failure and that has claimed its own dignity being markedly different from heart failure with reduced EF in terms of etiology and natural history (Graziani et al., 2018). Recently, a growing body of evidence points the finger toward microvascular dysfunction as the major determinant of the pathological cascade that justifies clinical manifestations (Crea et al., 2017). The high burden of comorbidities such as metabolic syndrome, hypertension, atrial fibrillation, chronic kidney disease, obstructive sleep apnea, and similar, could lead to a systemic inflammatory state that impacts the physiology of the endothelium and the perivascular environment, engaging complex molecular pathways that ultimately converge to myocardial fibrosis, stiffening, and dysfunction (Paulus and Tschope, 2013). These changes could even self-perpetrate with a positive feedback where hypoxia and locally released inflammatory cytokines trigger interstitial fibrosis and hypertrophy (Ohanyan et al., 2018). Identifying microvascular dysfunction both as the cause and the maintenance mechanism of this condition has opened the field to explore specific pharmacological targets like nitric oxide (NO) pathway, sarcomeric titin, transforming growth factor beta (TGF-β) pathway, immunomodulators or adenosine receptors, trying to tackle the endothelial impairment that lies in the background of this syndrome (Graziani et al., 2018 ; Lam et al., 2018). Yet, many questions remain, and the new data collected still lack a translation to improved treatment strategies. To further elaborate on this tangled and exponentially growing topic, we will review the evidence favoring a microvasculature-driven etiology of this condition, its clinical correlations, the proposed diagnostic workup, and the available/hypothesized therapeutic options to address microvascular dysfunction in the failing heart.