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Background: Patient-related and lesion-related factors may influence instantaneous wave-free ratio (iFR)/fractional flow reserve (FFR) concordance, potentially affecting the safety of revascularization deferral., Methods: Consecutive patients with at least an intermediate coronary stenosis evaluated by both iFR and FFR were retrospectively enrolled. The agreement between iFR and FFR at their diagnostic cut-offs (FFR 0.80, iFR 0.89) was assessed. Predictors of discordance were assessed using multivariate analyses. Tailored iFR cut-offs according to predictors of discordance best matching an FFR of 0.80 were identified. The impact of reclassification according to tailored iFR cut-offs on major cardiovascular events (MACE: cardiovascular death, myocardial infarction or target-lesion revascularization) among deferred lesions was investigated., Results: Two hundred and ninety-nine intermediate coronary stenosis [FFR 0.84 (0.78-0.89), iFR 0.91 (0.87-0.95), 202 left main/left anterior descending (LM/LAD) vessels, 67.6%] of 260 patients were studied. Discordance rate was 23.4% (n = 70, 10.7% iFR-negative discordant, 12.7% iFR-positive discordant). Predictors of discordance were LM/LAD disease, multivessel disease, non-ST-elevation myocardial infarction, smoking, reduced eGFR and hypertension. Lesion reclassification with tailored iFR cut-offs based on patient-level predictors carried no prognostic value among deferred lesions. Reclassification according to lesion location, which was entirely driven by LM/LAD lesions (iFR cut-offs: 0.93 for LM/LAD, 0.89 for non-LM/LAD), identified increased MACE among lesions deferred based on a negative FFR, between patients with a positive as compared with a negative iFR (19.4 vs. 6.1%, P = 0.044), whereas the same association was not observed with the conventional 0.89 iFR cut-off (15 vs. 8.6%, P = 0.303)., Conclusion: Tailored vessel-based iFR cut-offs carry prognostic value among FFR-negative lesions, suggesting that a one-size-fit-all iFR cut-off might be clinically unsatisfactory., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Aims: Radiation use in medicine has significantly increased over the last decade, and cardiologists are among the specialists most responsible for X-ray exposure. The present study investigates a broad range of aspects, from specific European Union directives to general practical principles, related to radiation management among a national cohort of cardiologists., Methods and Results: A voluntary 31-question survey was run on the Italian Arrhythmology and Pacing Society (AIAC) website. From June 2019 to January 2020, 125 cardiologists, routinely performing interventional electrophysiology, participated in the survey. Eighty-seven (70.2%) participants are aware of the recent European Directive (Euratom 2013/59), although only 35 (28.2%) declare to have read the document in detail. Ninety-six (77.4%) participants register the dose delivered to the patient in each procedure, in 66.1% of the cases both as fluoroscopy time and dose area product. Years of exposition (P = 0.009) and working in centers performing pediatric procedures (P = 0.021) related to greater degree of X-ray equipment optimization. The majority of participants (72, 58.1%) did not recently attend radioprotection courses. The latter is related to increased awareness of techniques to reduce radiation exposure (96% vs. 81%, P = 0.022), registration of the delivered dose in each procedure (92% vs. 67%, P = 0.009), and X-ray equipment optimization (50% vs. 36%, P = 0.006)., Conclusion: Italian interventional cardiologists show an acceptable level of radiation awareness and knowledge of updated European directives. However, there is clear space for improvement. Comparison to other health professionals, both at national and international levels, is needed to pursue proper X-ray management and protect public health., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Aims: Colchicine has an emerging role in the cardiovascular field, although, concerns for side effects, especially gastrointestinal, limit its prescription. We aimed at evaluating reported side effects of colchicine for cardiovascular indications., Methods: We performed a meta-analysis of published randomized controlled trials on colchicine for the treatment of cardiovascular diseases. Random-effects meta-analysis was used to assess the risk of adverse events and drug withdrawal. Publication bias was assessed using the Egger test, and meta-regression was performed to assess sources of heterogeneity., Results: Among 14 188 patients, 7136 patients received colchicine while the other 7052 received placebo. The occurrence of any adverse event with colchicine was reported in 15.3 vs. 13.9% patients [relative risk (RR) 1.26, 95% confidence interval (CI) 0.96-1.64, P = 0.09]. Gastrointestinal events were reported in 16.1 vs. 12.2% (RR 2.16, 95% CI 1.50-3.12, P < 0.001), while diarrhea was reported in 12.5 vs. 8.1% (RR 2.77, 95% CI 1.55-4.94, P < 0.001). The risk of gastrointestinal events increased with daily dose and shorter treatment duration. Myalgias were observed in 21 vs. 18% patients (RR 1.16, 95% CI 1.02-1.32, P = 0.03). Other adverse events such as myotoxicity, hepatic adverse events, hematologic adverse events, cutaneous adverse events, infection or death were not increased by colchicine treatment. Colchicine discontinuation was reported in 4.8 vs. 3.4% patients (RR 1.54, 95% CI 1.20-1.99, P < 0.001)., Conclusion: Colchicine is associated with increased risk of gastrointestinal events and myalgias, but not of other adverse events. The risk of gastrointestinal events may be avoided with lower dose (0.5 mg/daily) and is inversely related to treatment duration, possibly due to early drug discontinuation or drug tolerance., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: The clinical impact of stent strut thickness in coronary bifurcation lesions in small vessels has not been assessed in a real-world population., Methods: All 506 patients enrolled in the RAIN study, undergoing PCI in a vessel with a diameter 2.5 mm or less were retrospectively evaluated and divided into two groups according to stent strut thickness: 74 μm (n = 206) versus 81 μm (n = 300); 87.1% of the lesions involved bifurcations. TLF [defined as a composite of myocardial infarction (MI) and target lesion revascularization (TLR)] was the primary endpoint, with MACE (a composite of death, MI and TLR), its components and stent thrombosis the secondary endpoint., Results: After 16 (14-18) months, a lower incidence of TLF (4.3 vs. 9.8%, P = 0.026) and ST (1.0 vs. 3.0%, P = 0.042) was seen in the 74 μm group, whereas MACE occurred in 60 of 506 patients, with no statistical difference between the two groups (9.7 vs. 13.3%, P = 0.070). At multivariate analysis, chronic renal failure increased the risk of TLF while thinner strut was an independent protective factor (hazard ratio 0.51, CI 0.17-0.85, P = 0.005)., Conclusion: In this real-world population, patients being treated for small vessels lesions with thinner strut stents had lower rates of TLF, MI and ST.

: Well known in past centuries as a herbal remedy for osteoarticular pain and commonly used in the treatment of gout and familial Mediterranean fever, colchicine has an emerging role in the setting of cardiovascular diseases. Its unique properties not only target the key mechanisms of recurrent inflammation underlying pericardial syndromes but also inflammation within atherosclerotic plaques, atrial fibrillation recurrence and adverse ventricular remodelling leading to heart failure.The effect of colchicine in the treatment of cardiovascular diseases along with essential pharmacology will be discussed, reviewing the most important and recent clinical studies. Colchicine is a valuable, well tolerated and inexpensive drug in the setting of cardiovascular diseases.

Aim: To report the Italian data deriving from the European Society of Cardiology-EURObservational Research Program atrial fibrillation ablation long-term registry., Methods and Results: Ten Italian centers enrolled up to 50 consecutive patients undergoing atrial fibrillation ablation. Of the 318 patients included, 5 (1.6%) did not undergo catheter ablation, 1 had ablation partially done and 62 were lost at 1-year follow-up. Women were less represented (23.6%) and the median age was 60.0 years. A total of 195 patients (62.3%) suffered paroxysmal atrial fibrillation, whereas only 9 (2.9%) had long-standing persistent atrial fibrillation. Most Italian patients (92.3%) were symptomatic but suffering fewer symptomatic events than patients enrolled in other countries (median of two events in the month preceding the ablation vs. three, respectively; P < 0.0001). The main finding of the study is that the success rate at 1 year, with and without antiarrhythmic drugs, was 76.4%, consistently with other participating countries (73.4%). This result was obtained however, with a significantly lower prevalence of 1-year adverse events (7.3 vs. 16.6%, P < 0.0001). Procedure duration and fluoroscopy total time resulted as being shorter in Italy (145 vs. 160, P = 0.0005 and 16.9 vs. 20.0 min, P = 0.0018, respectively); however, the radiation dose per BSA was greater (37.5 vs. 26.0 mGy/cm, P = 0.0022)., Conclusion: The demographic characteristics of patients undergoing atrial fibrillation ablation are similar to those reported in other countries. The success rate in Italy is consistent with those in other countries, whereas the complications rate is lower.

Introduction: The impact on clinical outcomes of the metal coverage on the coronary surface (namely the metal-to-artery ratio) of currently used drug-eluting stents (DESs) has not been defined., Methods: All patients with a left main or bifurcation stenosis treated with percutaneous coronary intervention (PCI) using ultrathin stents (struts thinner than 81 μm) were enrolled with a prospective multicentre fashion. The rate of device-oriented endpoint [DOE, defined as a composite of target lesion revascularization (TLR) and stent thrombosis] was the primary endpoint, while its single components were the secondary ones, evaluated according to the metal-to-artery ratio., Results: After 14 ± 10.4 months 62 (7.5%) of 830 patients undergoing PCI on left main experienced a DOE without differences in the metal-to-artery ratio (14.5 ± 2.1 vs. 14.4 ± 1.9, P = 0.51). Fifty out (2.4%) of 2082 patients treated with PCI on a coronary bifurcation other than left main experienced a DOE, with a higher mean metal-to-artery ratio (15.3 ± 2.1 vs. 14.6 ± 2, P = 0.01). At multivariate analysis, together with hypertension and diabetes, the metal-to-artery ratio was an independent predictor of DOE (hazard ratio 1.7 : 1.02-1.34, P = 0.02) in nonleft main PCI. When analysed for diameter, we found a significant correlation with DOE when the stent diameter was inferior to 3.0 mm (hazard ratio 1.21: 1.06-1.38, P < 0.01, all 95% confidence interval); this result was mainly consistent for patients treated with provisional stenting. The metal-to-artery ratio does not impact on outcomes in left main PCI, both in the provisional or two-stent technique, and generally when a drug-eluting stent more than 3.5 mm in diameter is implanted. Regarding nonleft main PCI, it is independently related to DOE and TLR, especially for DES with a diameter of 3.25 mm or less., Conclusion: The metal-to-artery ratio does not impact on outcomes in left main PCI, both in the provisional or two-stent technique, and generally when a drug-eluting stent more than 3.5 mm in diameter is implanted. Regarding nonleft main PCI, it is independently related to DOE and TLR, especially for DES with a diameter of 3.25 mm or less.

: The COVID-19 pandemic is challenging our cardiovascular care of patients with heart diseases. In the setting of pericardial diseases, there are two possible different scenarios to consider: the patient being treated for pericarditis who subsequently becomes infected with SARS-CoV-2, and the patient with COVID-19 who develops pericarditis or pericardial effusion. In both conditions, clinicians may be doubtful regarding the safety of nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, colchicine, and biological agents, such as anti-IL1 agents (e.g. anakinra), that are the mainstay of therapy for pericarditis.For NSAIDs, there is no clear scientific evidence linking ibuprofen and other NSAIDs to worsening of COVID-19; however, it seems prudent to continue them, if necessary to control pericarditis, and on the other hand, to prefer paracetamol for fever and systemic symptoms related to COVID-19. Treatments with corticosteroids, colchicine, and anakinra appear well tolerated in the context of COVID-19 infection and are currently actively evaluated as potential therapeutic options for COVID infection at different stages of the disease. On this basis, currently most treatments for pericarditis do not appear contraindicated also in the presence of possible COVID-19 infection and should not be discontinued, and some (corticosteroids, colchicine, and anakinra) can be considered to treat both conditions.

Background: Atrial arrhythmias are common following noncardiac thoracic surgery. In particular, early postoperative atrial arrhythmias after lung transplantation are very frequent, especially atrial fibrillation (AFib). Late atrial arrhythmia occurrence following lung transplantation, instead, has been less commonly reported., Methods: The aim of the present systematic review and meta-analysis is to analyse the incidence rate of late atrial arrhythmia and AFib in lung transplantation patients, with a special focus on double lung transplant (DLT), also to assess potential predictors of AFib occurrence. After bibliographic search (PUBMED/Medline and Embase databases), a random-effect model meta-analysis was performed: seven studies were finally included, including 2068 lung transplantation patients., Results: The pooled incidence rate of late atrial arrhythmia was 4.3%/year [95% confidence interval (CI) 2.8-6.1%/year, I = 69%], whereas late AFib incidence rate was 1.5%/year (95% CI 0.7-2.6%/year, I = 87%). In patients undergoing DLT, the pooled incidence rate of late atrial arrhythmia was 4.1%/year (95% CI 2.5-6.0%/year, I = 67%), while the AFib incidence rate was 0.9%/year (95% CI 0.1-2.4%/year, I = 92%). A longer follow-up duration significantly related to the reduced incidence rate of AFib (P = 0.02). History of AFib (hazard ratio 11.2, 95% CI 5.9-21.3) and early postoperative AFib (hazard ratio 10.3, 95% CI 5.9-18.0) emerged, instead, as relevant predictors of AFib occurrence., Conclusion: Late atrial arrhythmia occurrence is not infrequent in lung transplantation patients; however, late Afib incidence was rare and showed a time-dependent decrease, particularly in DLT patients, suggesting that a transmural pulmonary veins isolation, the mainstay of transcatheter ablation, is effective in decreasing the likelihood of experiencing AFib.

Aims: To systematically review literature comparing bare metal stent (BMS) to drug-eluting stent (DES) in end-stage renal disease (ESRD) patients on dialysis. ESRD patients on dialysis often suffer from accelerated atherosclerosis and higher rate of stent-related complications including major adverse cardiovascular events. Because dialysis usually qualifies ineligibility for randomized clinical trials, an evidenced-based stent choice for these patients is scarce., Methods: PUBMED, CINHAL, COCHRANE, EMBASE and WEB OF SCIENCE were searched for studies comparing BMS vs. DES outcome in ESRD patients on dialysis., Results: Twenty studies including 64 232 patients were considered. The use of DES was significantly associated with a reduction in all-cause mortality [odds ratio (OR) 0.83, 95% confidence interval (CI) 0.76-0.89], death from a cardiovascular cause (OR 0.80, 95% CI 0.76-0.84) and target lesion revascularization/target vessel revascularization (OR 0.73, 95% CI 0.53-1.00). No significant difference was found in stent thrombosis (OR 1.08, 95% CI 0.50-2.33) and myocardial infarction incidence (OR 0.91, 95% CI 0.69-1.20)., Conclusions: Our meta-analysis shows a significant reduction in all-cause and cardiovascular mortality with the use of DES over BMS in dialyzed patients. Despite the lack of randomized studies, systematic use of DES in these high-risk patients should thus reasonably be considered as a first option in percutaneous coronary intervention candidates.

Aims: The analysis evaluated the contemporary percentage of patients with established coronary heart disease (CHD) reaching the European guidelines recommended LDL-cholesterol (LDL-C) levels of less than 70 mg/dl and the threshold required for proprotein convertase subtlisin/kexin type 9 reimbursement in Italy (100 mg/dl). It also assessed how these percentages would change in case of diffuse use of ezetimibe., Methods: The Dyslipidemia International Study II enrolled CHD patients aged at least 18 either on lipid-lowering therapy (LLT) for at least 3 months or not on LLT at the time of the lipid profile. Distribution of LLTs and LDL-C target attainment were assessed. Multivariate logistic regression evaluated predictors of LDL-C target attainment. A 24% LDL-C lowering was modeled in patients not taking ezetimibe to assess its potential effects., Results: Among 676 Italian CHD patients enrolled, LDL-C concentrations were lower among the 631 patients (93.3%) who were on LLT (82 versus 118 mg/dl; P < 0.001). The LDL-C target was attained by 35.4% of patients. Statin dose (median atorvastatin dose 40 mg/day) was the sole significant predictor of LDL-C target attainment. The simple addition of ezetimibe in the model reduced the percentage of patients more than 70 and 100 mg/dl from 64.6 to 37.9% and from 25.1 to 11.8%, respectively., Conclusion: Despite treatment in more than 90%, only one-third of Italian stable CHD patients attained the recommended LDL-C target. Statin dose was the sole predictor of the target achievement. The addition of ezetimibe would almost double patients at target and halve the potential candidates for reimbursement of more expensive agents such as proprotein convertase subtlisin/kexin type 9 inhibitors.

Aims: About one-third of ischemic stroke are cryptogenic. Paradoxical embolism through patent foramen ovale (PFO) has been identified as a possible cause of cryptogenic stroke. Therefore, PFO closure has been considered for secondary prevention of cryptogenic stroke. However, randomized clinical trials (RCTs) comparing PFO closure versus medical therapy led to conflicting results. Our objectives were to examine if PFO closure is superior to medical therapy alone for secondary prevention of cryptogenic stroke and to investigate whether PFO closure is associated with an increased incidence of atrial fibrillation/atrial flutter (AFL)., Methods: The authors systematically searched MEDLINE for RCTs that compared PFO closure with medical therapy. Efficacy outcome was cerebrovascular event (CVE) recurrence and safety outcome was new-onset atrial fibrillation/AFL. The outcomes of interest were investigated according to device type with subgroup analyses and meta-regression., Results: The authors included eight RCTs constituting 4114 patients. Patients who underwent PFO closure had a lower risk of CVE recurrence compared with medically treated patients [relative risk (RR): 0.56; 95% confidence interval (CI) 0.40-0.80; P = 0.001; I = 30%]. This protective effect was consistent across the different device types. Patients who underwent PFO closure developed more frequently atrial fibrillation/AFL (RR 4.96; 95% CI 2.74-8.99; P < 0.00001; I = 0%), which was mainly transient and within 1 month. Atrial fibrillation/AFL risk was consistent according to device types, although marginally significant in the Amplatzer subgroup., Conclusion: PFO closure might have a role in secondary CVE prevention of patients with PFO and cryptogenic stroke. However, it is associated with an increased incidence of new-onset atrial fibrillation/AFL especially within 1 month.

Aims: Elevated serum uric acid (eSUA) was associated with unfavorable outcome in patients with ST-segment elevation myocardial infarction (STEMI). However, the effect of eSUA on myocardial reperfusion injury and infarct size has been poorly investigated. Our aim was to correlate eSUA with infarct size, infarct size shrinkage, myocardial reperfusion grade and long-term mortality in STEMI patients undergoing primary percutaneous coronary intervention., Methods: We performed a post-hoc patients-level analysis of two randomized controlled trials, testing strategies for myocardial ischemia/reperfusion injury protection. Each patient underwent acute (3-5 days) and follow-up (4-6 months) cardiac magnetic resonance. Infarct size and infarct size shrinkage were outcomes of interest. We assessed T2-weighted edema, myocardial blush grade (MBG), corrected Thrombolysis in myocardial infarction Frame Count, ST-segment resolution and long-term all-cause mortality., Results: A total of 101 (86.1% anterior) STEMI patients were included; eSUA was found in 16 (15.8%) patients. Infarct size was larger in eSUA compared with non-eSUA patients (42.3 ± 22 vs. 29.1 ± 15 ml, P = 0.008). After adjusting for covariates, infarct size was 10.3 ml (95% confidence interval 1.2-19.3 ml, P = 0.001) larger in eSUA. Among patients with anterior myocardial infarction the difference in delayed enhancement between groups was maintained (respectively, 42.3 ± 22.4 vs. 29.9 ± 15.4 ml, P = 0.015). Infarct size shrinkage was similar between the groups. Compared with non-eSUA, eSUA patients had larger T2-weighted edema (53.8 vs. 41.2 ml, P = 0.031) and less favorable MBG (MBG < 2: 44.4 vs. 13.6%, P = 0.045). Corrected Thrombolysis in myocardial infarction Frame Count and ST-segment resolution did not significantly differ between the groups. At a median follow-up of 7.3 years, all-cause mortality was higher in the eSUA group (18.8 vs. 2.4%, P = 0.028)., Conclusion: eSUA may affect myocardial reperfusion in patients with STEMI undergoing percutaneous coronary intervention and is associated with larger infarct size and higher long-term mortality.

Objectives: We assessed the clinical profile of patients with acute coronary syndrome (ACS) and nonobstructive coronary artery disease (CAD) in a real world setting, focusing on pattern of care and on prognosis., Methods: Each nonobstructive CAD (<50% stenosis in any epicardial coronary artery) patient was matched with an obstructive CAD patient; adjusted estimates of prescription of guideline-recommended drugs at discharge and of long-term prognosis were evaluated., Results: Among 2995 consecutive ACS patients who underwent coronary angiography, 125 (4.2%) had nonobstructive CAD. Nonobstructive CAD patients had significantly lower odds of receiving aspirin [odds ratio (OR) 0.31, 95% confidence interval (CI): 0.14-0.68], thienopyridines (OR 0.01, 95% CI: 0.00-0.07), statins (OR 0.31, 95% CI: 0.17-0.58), beta-blockers (OR 0.32, 95% CI: 0.17-0.63) and angiotensin converting enzyme-inhibitors /angiotensin receptor blockers (OR 0.36, 95% CI: 0.17-0.91) compared with matched patients. During a 3-year follow-up, nonobstructive CAD patients had significantly fewer cardiovascular deaths and myocardial infarctions but numerically more episodes of unstable angina., Conclusions: The prevalence of nonobstructive CAD appears lower (4.2%) compared with published data. After extensive adjustment, patients with nonobstructive CAD were significantly less likely to be treated with guideline-recommended therapy, including aspirin and statins. Multicenter prospective studies targeting this specific population and the potential benefit of guideline-recommended therapies appear warranted.

Background: Although a more favorable neurohormonal balance may contribute to improving symptoms following cardiac resynchronization therapy (CRT), no information is available regarding the effects of CRT on insulin-like growth factor-1 (IGF-1). This study assessed the effects of CRT on IGF-1 levels and their correlation with changes in quality of life and left ventricular (LV) function., Methods and Results: Patients with cardiomyopathy in New York Heart Association class III or IV (n = 18; age 71 +/- 10 years), left ventricular ejection fraction (LVEF) < or = 40% and QRS > or = 130 ms or ventricular dyssynchrony were enrolled in the study and followed up for 6 months. After 3 months, there was an improvement in LVEF (from 29 +/- 7 to 33 +/- 10%, P = 0.0136) and quality of life (from 33 +/- 14 to 13 +/- 12, P = 0.0000) and an increase in IGF-1 levels (from 137 +/- 79 to 175 +/- 111 ng/ml, P = 0.01353). The change in quality of life correlated with changes in IGF-1 levels (P = 0.02) but not with LVEF changes., Conclusions: In patients with advanced heart failure, CRT leads to a significant increase in plasma IGF-1 levels within 3 months. This increase is correlated with the improvement in quality of life, whereas the increase in LVEF is not. This finding suggests that IGF-1 may play a role as a mediator in the early phase of symptomatic improvement after CRT.