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Summary Polymorphisms in the regulatory and intronic regions of several cytokines have been associated with differential cytokine production. In this paper we genotyped, using the polymerase chain reaction–sequence-specific primers (PCR-SSP) method, a series of 363 healthy Italian Caucasians with the aim of obtaining a reference population for further studies on the role of cytokines in the inflammatory and immune responses. We also compared the results to those for other populations. The polymorphisms analysed were those of tumour necrosis factor alpha (TNFA), interleukin 6 (IL-6), interleukin 10 (IL-10) and interferon gamma (IFNG). We found that the frequency of allele TNFA*1 at position -380 was 87.7% and that of TNFA*2 was 12.4%, significantly different from those of the UK and Japanese populations but not different from that of a population in Gambia. For IL-10 the frequencies of alleles -1082A and -1082G were 63.0% and 37.0% and those of alleles -819C, - 819T, -592C and -592A were 70.8, 29.2, 70.8 and 29.2%, respectively, significantly different from those observed in south-east England, in Manchester and in an Oriental population from southern China. The frequencies of IL-6 alleles - 174C and -174G were 29.0 and 71.0%, respectively; for IFNG polymorphisms at position -874, in the population under evaluation, the alleles -874T and -874A were present in 44.7 and 55.3% of the subjects, respectively. Genotype frequencies of IL-6 were significantly different from those observed in populations from Germany and from the UK. The analysis carried out by our group indicates that there is heterogeneity in the frequencies of the cytokine polymorphisms among the different Caucasian populations, and this underlines the importance of a ‘local’ reference population when evaluating the clinical relevance of cytokine gene polymorphisms. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy of renal transplantation in small pediatric patients, we have reviewed 41 allografts performed in 39 children (28 M/11 F) less than 6 years of age between 1987 and 1998 in the North Italy Transplant Program. Of these patients, 39 had a cadaver donor and 2 a living-related donor, with ages ranging from 20 days to 35 years. The mean follow-up was 56 months. Graft survival was 74.5% and 70.5% at 1 and 5 years, respectively. The causes of graft lost were acute rejection (4), graft vascular thrombosis (4), and hemolytic uremic syndrome recurrence (1). Only 1 patient has died due to chickenpox. Double and triple immunosuppressive therapies were used in 63% and 37% of patients, respectively, on the basis of different center protocols, without differences in graft survival. Steroids were successfully administered on alternate days in 37% of patients, 6-12 months after transplantation. Thrombosis was reported in 2 of 6 kidneys from donors less than 1 year of age and in 2 of 35 donors older than 1 year (P<0.05). Thirty rejections occurred in 23 patients: 7 episodes were steroid resistant and were treated with ATG/OKT3. Thirty-four infections were reported in 16 of 41 patients; of these 17 were viral, 14 bacterial, and 3 due to Mycoplasma. Four surgical complications were reported: 1 graft artery stenosis, 1 ureteral stenosis, 1 urinary leak, and 1 lymphocele. Mean height standard deviation score improved from −2.0±1.3 pre transplantation to &minus1.8±1.4, −1.5±1.3, and −1.5±1.5 at 1, 2, and 5 years post transplantation. Linear growth was significantly better in infants treated with alternate-day steroids. Hypertension was a frequent complication, since 19 of the 30 patients with a 5-year follow-up were still being treated with antihypertensive drugs. In conclusion, graft survival in patients less than 6 years old is satisfactory and similar to that obtained in children aged from 6 to 18 years (70... [ABSTRACT FROM AUTHOR]

Two novel human leucocyte antigen (HLA) class I alleles were characterized by means of sequencing-based typing techniques. HLA-A*310103 was identified in a cord blood unit from a Caucasoid individual. The sequence of this allele is identical to that of HLA-A*310102 except for a silent mutation in exon 3 at position 480 (G → A). HLA-B*9531 was found in a Caucasoid female patient registered on the heart transplantation waiting list in the North Italy Transplant programme. This new variant differs from HLA-B*1503 at position 572 (G → C) in exon 3. This nucleotide change leads to an amino acidic substitution at codon 167 from tryptophan to serine. [ABSTRACT FROM AUTHOR]

In this brief communication, we describe a novel human leukocyte antigen-B (HLA-B) allele (HLA-B*1819). This allele, found in an Italian Caucasian individual, differs from HLA-B*180101 by three nucleotide changes in exon 3. These mutations are located at positions 527, 538, and 539 where a T, a C, and a T are substituted respectively, by an A, a T, and a G, leading to three aminoacidic substitutions at codon 152 from Valine to Glutamic Acid (GTG→GAG), at codon 155 from Histidine to Glutamine (CAC→CAG), and at codon 156 from Cysteine to Tryptophan (TGT→TGG). [ABSTRACT FROM AUTHOR]

We report here the exon 2 sequence of the novel HLA-DRB1*110403 which differs from DRB1*110401 by a single synonymous nucleotide substitution at codon 78, where TAC is substituted by TAT. The variant originally identified in a Caucasoid individual was confirmed by cloning and sequencing. [ABSTRACT FROM AUTHOR]

A new HLA-B allele, B*5615, has been identified in a Caucasian individual by sequence-based typing. This allele shows a sequence identical to that of HLA-B*5601 except for two nucleotide substitutions that cause a change from TTA to TAC at codon 116 and an amino acidic change from Leucine to Tyrosine in the mature protein. [ABSTRACT FROM AUTHOR]

We report herein the identification of a new HLA-DRB1 allele, DRB1*0707. This new allele was seen in a volunteer bone marrow donor (ID#118069) belonging to the German bone marrow donor registry (DKMS). HLA-DRB1*0707 was detected while performing HLA-DRB1 high resolution typing by sequence based typing. This novel allele differs from DRB1*070101 by a single nucleotide substitution at position 163 (C→T) in exon 2. [ABSTRACT FROM AUTHOR]

In this report we describe a new HLA-DRB1 allele, DRB1*1353, which was initially recognized by a discrepancy between the results obtained with polymerase chain reaction using sequence-specific oligonucleotide (PCR-SSO) and sequence-specific primers (PCR-SSP). Sequence-based typing revealed sequence differences with other known HLA-DRB1 alleles. DRB1*1353 is identical to DRB1*13011 except for two nucleotide substitutions at nucleotide 84 (C(r)G) and at nucleotide 140 (T(r)A). These differences give rise to two amino acid substitutions at codons 28 and 47 from Asp to Glu and from Phe to Tyr, respectively. [ABSTRACT FROM AUTHOR]

We report the identification of a novel DRB3*02 using sequence-based typing (SBT). This new allele, officially named DRB3*0217, was detected while performing HLA high resolution typing of a bone marrow recipient and his siblings. DNA sequencing demonstrated the presence of a nucleotide substitution in exon 2 at position 199 where a C was substituted by a T. This point mutation at codon 67 (CTC→TTC) has resulted in an amino acid substitution from Leucine to Phenylalanine. [ABSTRACT FROM AUTHOR]

Abstract: We report the identification of a novel DRB1*11 using sequence-based typing. This new allele, officially named DRB1*1139, was detected while performing HLA-DRB1 high-resolution typing of a volunteer bone marrow donor. DRB1*1139 is identical to DRB1*11011 except at codon 51 (ACG→AGG) changing the encoded Threonine to Arginine. The triplet AGG has never been found in any other DRB1 allele. In fact, with standard polymerase chain reaction (PCR) amplification with sequence specific primers, the presented allele would have been interpreted as DRB1*1101 (Note). [ABSTRACT FROM AUTHOR]

Abstract: We report herein the identification of HLA-B*4902. This new allele was identified in a Caucasian individual serologically typed as B49. The allele codifying for this antigen was not clearly detectable with poly-merase chain reaction using sequence-specific primers (PCR-SSP) because of an atypical amplification pattern. DNA sequencing demonstrated the pres-ence of a new variant due to two nucleotide substitutions (from G to C and from T to C) in exon 2 at nucleotides 309 and 311 respectively. These substitutions would result in a silent mutation and in one amino acid substi-tution from Ile to Thr, respectively. [ABSTRACT FROM AUTHOR]

Background: In asymptomatic patients presenting with significant internal carotid artery (ICA) stenoses undergoing endovascular revascularization, a selective angiography before stenting (CAS) is required. Sometimes, angiographic findings could be discordant from non-invasive assessment and a tool able to evaluate functional relevance of the stenosis could be of value. We sought to evaluate the usefulness of quantitative flow ratio (QFR) as angiography-based tool for functional assessment of ICA stenoses., Methods: We prospectively enrolled 50 asymptomatic patients undergoing CAS. Peak systolic velocity (PSV, cm/s) assessed at color Doppler echocardiography was used to identify significant stenoses (PSV >125 cm/s). At angiography, assessment of ICA stenosis was obtained visually (%DSVISUAL) and according NASCET criteria (%DSNASCET). Stenoses were considered significant if >60%. After exclusion of 20 vessels, QFR, area stenosis (AS, %) and minimal lumen area (MLA, mm 2 ) were obtained in the remaining 80 vessels., Results: At linear regression analysis, QFR significantly correlated with PSV (r 2 =0.52, P<0.001) as well as with %DSNASCET (r 2 =0.68, P<0.001) and %DSVISUAL (r 2 =0.71, P<0.001). Using PSV as reference, QFR showed good accuracy to predict functionally significant stenosis (AUC=0.98, P<0.001) with a cut-off value of 0.93. As compared with %DSNASCET and %DSVISUAL, QFR showed a significantly higher accuracy (61% vs. 73% vs. 94%, respectively; P<0.05), sensitivity (43% vs. 61% vs. 93%, respectively; P<0.05) and negative predictive value (46% vs. 51% vs. 85%, respectively; P<0.05) for detecting hemodynamically significant ICA stenoses., Conclusions: This study suggest the potential benefit of adopting QFR for functional assessment of extracranial ICA stenoses. These data should be validated in larger studies.

Several scores can predict clinical outcomes of patients with Acute Coronary Syndromes (ACS). The validated PARIS (Patterns of Non-Adherence to Anti-Platelet Regimen in Stented Patients) score is poorly used in clinical practice because it needs items that are not always easily available. The ACEF (Age, Creatinine, and Ejection Fraction) score is more attractive because it only includes three items. We compared these scores to risk-stratify ACS patients enrolled into the START (Survey on anticoagulated pAtients RegisTer)-ANTIPLATELET registry. ACS patients who completed 1-year follow-up ( n = 1171) were grouped in tertiles (low, medium, and high-risk) according to their ACEF/PARIS scores. Primary endpoints were: one-year MACCE (major adverse cardiac and cerebrovascular events: death, non-fatal myocardial infarction, stroke or target vessel revascularization) and NACE (net adverse cardiac and cerebrovascular events): MACCE plus major bleeding). MACCE incidence was higher in the high-risk tertile (15%) VS low/medium (3/7 %) risk tertiles ( P < .001). NACE incidence in the high-risk tertile was 24% VS low/medium (9/15 %) risk tertiles ( P < .001), independently of the risk score used . The ACEF score has similar accuracy as the validated PARIS score for the estimation of ischemic/bleeding risk. Thereby, we strongly suggest its use in clinical practice to risk-stratify ACS patients and select optimal therapeutic strategies., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Although the use of rotational atherectomy (RA) is off-label in the setting of ST-elevation myocardial infarction (STEMI), it can be the only option in severely calcified culprit lesions to achieve procedural success. We sought to investigate the safety and feasibility of RA during primary percutaneous coronary intervention (PPCI)., Methods: This was a retrospective observational study of patients who underwent RA during PPCI from 12 European centres. The main outcomes were procedural success (defined as successful stent implantation with final thrombolysis in myocardial infarction [TIMI] flow 3 and residual stenosis < 30%) and in-hospital mortality. A comparison of patients presenting with and without shock was performed., Results: In 104 patients with RA during STEMI, the mean age was 72.8 ± 9.1 years, and 35% presented with cardiogenic shock. Bailout RA was performed in 76.9% of cases. Mean burr size was 1.42 ± 0.21 mm. Procedural success was achieved in 86.5% of cases, with no difference between shocked and nonshocked patients (94.4% vs 82.4%; P = 0.13). In-hospital stent thrombosis occurred in 0.96%, perforation in 1.9% and burr entrapment in 2.9% of cases. In spite of equally high procedural success, in-hospital mortality was higher in shocked (50%) compared with nonshocked patients (1.5%; P < 0.0001)., Conclusions: Patients presenting with STEMI requiring RA, represent a high-risk population, frequently presenting with cardiogenic shock. In this analysis of selected patients, RA was performed as a bailout strategy in the majority, and, as such, RA seems to be feasible with a high procedural success rate. In the absence of cardiogenic shock, RA-facilitated PCI seems to be associated with low in-hospital mortality., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The ISAR-REACT 5 trial compared the efficacy and safety of ticagrelor and prasugrel in patients with ACS managed invasively. The present study sought to investigate the impact of ticagrelor and prasugrel on the incidence and pattern of urgent revascularization in acute coronary syndromes (ACS) patients undergoing percutaneous coronary intervention (PCI)., Methods and Results: This post-hoc analysis of the ISAR-REACT 5 trial included all ACS patients who underwent PCI. The primary endpoint for this analysis was the incidence of urgent revascularization at 12-month follow-up. Secondary outcome was the pattern of urgent revascularization procedures (namely, urgent target vessel/non-target vessel revascularization - TVR/NTVR). Among 3,377 ACS patients who underwent PCI, 1,676 were assigned to ticagrelor and 1,701 to prasugrel before PCI. After 12 months, the incidence of urgent revascularization was higher among patients assigned to ticagrelor as compared to prasugrel (6.8% vs. 5.2%; hazard ratio [HR] = 1.32, 95% confidence interval [CI] 1.00-1.75; p = 0.051), mostly attributable to significantly more urgent NTVR in the ticagrelor group (3.8% vs. 2.4%; HR = 1.62 [1.09-2.41]; p = 0.017). The risk of urgent TVR did not differ between treatment groups (3.3% vs. 3.0%; HR = 1.13 [0.77-1.65]; p = 0.546)., Conclusions: In ACS patients treated with PCI, the cumulative rate of urgent revascularizations after 12 months is higher with ticagrelor compared to prasugrel, due to a significant increase in urgent revascularizations involving remote coronary vessels., (© 2024. The Author(s).)

Background: The performance of modified balloons (namely cutting or scoring balloons) to prepare severely calcified lesions in patients undergoing percutaneous coronary intervention (PCI) remains controversial. We investigated the clinical and imaging outcomes of patients undergoing PCI assigned to modified balloon therapy to prepare severely calcified coronary lesions before stent implantation., Methods: In this meta-analysis, we aggregated the study-level data from trials enrolling invasively treated patients who were randomly assigned to modified balloon or control therapy to prepare severely calcified lesions before stenting. The primary outcome was major adverse cardiac events (MACE), including death, myocardial infarction (MI), and repeat revascularization. The secondary outcomes included the individual components of the primary outcome, coronary perforation and final minimal stent area (MSA) as measured by intracoronary imaging., Results: A total of 648 participants in six trials were allocated to modified balloon therapy (n = 335) or control therapy (semi-compliant, non-compliant, or super high-pressure balloon, n = 313). The median follow-up was 11 months. Overall, MACE occurred in 8.96% of patients assigned to a modified balloon and 12.78% of patients assigned to control therapy [risk ratio = 0.70, 95% confidence interval (CI) 0.35-1.39; P = 0.24]. There was a significant treatment effect-by-modified balloon type interaction for the outcome MACE in patients assigned to cutting balloon compared with control therapy [RR = 0.40 (0.28-0.56), P for interaction (P int ) < 0.001]. Patients treated with a modified balloon compared with control therapy showed neither a significant difference for the other clinical outcomes nor for final MSA [standardized mean difference = 0.67 (- 0.71, 2.06); P = 0.26]., Conclusions: In patients treated with PCI for severely calcific coronary artery disease a strategy of lesion preparation with a modified balloon before stenting does not improve clinical or imaging outcomes compared with control therapy. The different performance of cutting and scoring balloons warrants further investigation., (© 2023. The Author(s).)

Introduction and Objectives: Multivessel percutaneous coronary intervention (MV-PCI) is recommended in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (CAD) without cardiogenic shock. The present network meta-analysis investigated the optimal timing of MV-PCI in this context., Methods: We pooled the aggregated data from randomized trials investigating stable STEMI patients with multivessel CAD treated with a strategy of either MV-PCI or culprit vessel-only PCI. The primary outcome was all-cause death. The main secondary outcomes were cardiovascular death, myocardial infarction, and unplanned ischemia-driven revascularization., Results: Among 11 trials, a total of 10 507 patients were randomly assigned to MV-PCI (same sitting, n=1683; staged during the index hospitalization, n=3460; staged during a subsequent hospitalization within 45 days, n=3275) or to culprit vessel-only PCI (n=2089). The median follow-up was 18.6 months. In comparison with culprit vessel-only PCI, MV-PCI staged during the index hospitalization significantly reduced all-cause death (risk ratio, 0.73; 95%CI, 0.56-0.92; P=.008) and ranked as possibly the best treatment option for this outcome compared with all other strategies. In comparison with culprit vessel-only PCI, a MV-PCI reduced cardiovascular mortality without differences dependent on the timing of revascularization. MV-PCI within the index hospitalization, either in a single procedure or staged, significantly reduced myocardial infarction and unplanned ischemia-driven revascularization, with no significant difference between each other., Conclusions: In patients with STEMI and multivessel CAD without cardiogenic shock, multivessel PCI within the index hospitalization, either in a single procedure or staged, represents the safest and most efficacious approach. The different timings of multivessel PCI did not result in any significant differences in all-cause death. This study is registered at PROSPERO (CRD42023457794)., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: Patent hemostasis (PH) is essential for preventing radial artery occlusion (RAO) after trans-radial procedures; however, it remains unclear how it should be obtained. The aim of this multicenter randomized study was to evaluate whether the use of an adjustable device (AD), inflated with a pre-determined amount of air (AoA), was more effective than a non-adjustable device (non-AD) for achieving PH, thereby reducing the incidence of RAO., Methods: We enrolled a total of 480 patients undergoing transradial procedure at 3 Italian institutions. Before the procedure, a modified Reverse Barbeau Test (mRBT) was performed in all patients to evaluate the AoA to be eventually inflated in the AD. After the procedure, patients were randomized into 2 groups: (1) AD Group, using TR-Band (Terumo) inflated with the pre-determined AoA; and 2) non-AD Group, using RadiStop (Abbott). An RBT was performed during compression to demonstrate the achievement of PH, as well as 24 hours later to evaluate the occurrence of RAO., Results: PH was more often obtained in the AD Group compared with the non-AD Group (90% vs 64%, respectively, P less than .001), with no difference in terms of bleedings. RAO occurred more often in the non-AD Group compared with the AD Group (10% vs 3%, respectively, P less than .001). Of note, mRBT was effective at guiding AD inflation and identifying high-risk patients in whom PH was more difficult to obtain., Conclusions: The use of AD, filled with a predetermined AoA, allowed PH significantly more often compared with non-AD, providing a significantly reduced incidence of RAO.

A significant proportion of patients presenting with signs and symptoms of myocardial ischemia have no "significant" epicardial disease; thereby, the assessment of coronary microcirculation gained an important role in improving diagnosis and guiding therapy. In fact, coronary microvascular dysfunction (CMD) could be found in a large proportion of these patients, supporting both symptoms and signs of myocardial ischemia. However, CMD represents a diagnostic challenge for two main reasons: (1) the small dimension of the coronary microvasculature prevents direct angiographic visualization, and (2) despite the availability of specific diagnostic tools, they remain invasive and underused in the current clinical practice. For these reasons, CMD remains underdiagnosed, and most of the patients remain with no specific treatment and quality-of-life-limiting symptoms. Of note, recent evidence suggests that a "full physiology" approach for the assessment of the whole coronary vasculature may offer a significant benefit in terms of symptom improvement among patients presenting with ischemia and non-obstructive coronary artery disease. We analyze the pathophysiology of coronary microvascular dysfunction, providing the readers with a guide for the invasive assessment of coronary microcirculation, together with the available evidence supporting its use in clinical practice.

Acute decompensation often represents the onset of symptoms associated with severe degenerative aortic stenosis (AS) and usually complicates the clinical course of the disease with a dismal impact on survival and quality of life. Several factors may derange the faint balance between left ventricular preload and afterload and precipitate the occurrence of symptoms and signs of acute heart failure (HF). A standardized approach for the management of this condition is currently lacking. Medical therapy finds very limited application in this setting, as drugs usually indicated for the control of acute HF might worsen hemodynamics in the presence of AS. Urgent aortic valve replacement is usually performed by transcatheter than surgical approach whereas, over the last decades, percutaneous balloon valvuloplasty gained renewed space as bridge to definitive therapy. This review focuses on the pathophysiological aspects of acute advanced AS and summarizes current evidence on its management., (© 2023. The Author(s).)

Background: The aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (De Ritis ratio), obtained from AST and ALT activities in the healthy range, has not been studied in association with mortality., Methods: This study included 3392 patients with stable coronary heart disease and aminotransferase activity in the reference range. Patients are categorized into two groups: a group with AST and ALT activity in the healthy range ( n = 1697), and a group with AST and/or ALT activity outside the healthy range but in the reference range ( n = 1695). The primary endpoint was all-cause mortality at three years., Results: The De Ritis ratio (median 5th-95th percentile] was 0.94 [0.61-1.41] in patients with AST and ALT in the healthy range and 0.93 [0.45-1.96] in patients with AST and/or ALT outside the healthy range ( p = 0.700). At three years, there were 86 deaths in patients with AST and ALT in the healthy range: 27 deaths (3.9%) in patients with a De Ritis ratio ≤median, and 59 deaths (8.2%) in patients with the De Ritis ratio >median (adjusted hazard ratio [HR] = 1.16, 95% confidence interval [CI] 0.94 to 1.42; p = 0.159); in patients with AST and/or ALT outside the healthy range, there were 148 deaths: 49 deaths (6.6%) in patients with a De Ritis ratio ≤median, and 99 deaths (14.1%) in patients with De Ritis ratio >median (adjusted HR = 1.27 [1.09-1.48], p = 0.002), with both HRs calculated per unit higher values of the De Ritis ratio., Conclusions: The De Ritis ratio obtained from AST and ALT activity in the healthy range was not independently associated with higher risk of mortality. The De Ritis ratio obtained from aminotransferase activity outside the healthy range (but still in the reference range) was independently associated with the risk of mortality.

Background: The treatment of drug-eluting stent (DES) in-stent restenosis (ISR) is challenging as it has a high risk of recurrence., Aims: The aim of this analysis was to develop and validate a model to predict the risk of repeat percutaneous coronary intervention (PCI) for recurrent DES-ISR., Methods: A retrospective, observational analysis was performed including consecutive patients treated with PCI for DES-ISR at two centres in Germany. Included patients were randomly divided into training and validation cohorts. Two regression analyses identified factors associated with repeat PCI for recurrent DES-ISR up to 1 year. The discriminative ability of the resultant model was then compared to a benchmark ISR classification model using bootstrap resampling. A classification and regression tree analysis and a numerical scoring system (the ISAR score) were used to predict the risk of repeat PCI for recurrent DES-ISR based on the identified predictors., Results: We included 1,986 patients in the current analysis, divided randomly into training (1,471 patients, 1,778 lesions) and validation (515 patients, 614 lesions) cohorts. Four factor variables (a non-focal ISR pattern, a time interval to ISR of <6 months, ISR of the left circumflex artery and ISR in a calcified vessel) were associated with repeat PCI for recurrent DES-ISR at 1-year follow-up. On bootstrap resampling analysis, the C-statistic for the model including these four variables was 0.60 (95% confidence interval [CI]: 0.57-0.63), whereas the C-statistic for the benchmark ISR classification model was 0.54 (95% CI: 0.52-0.57), a difference that was statistically significant (delta C-statistic 0.062; 95% CI: 0.035-0.094; p<0.001). The cumulative incidence of repeat PCI for recurrent DES-ISR was over three times higher in DES-ISR lesions with an ISAR score of ≥3 in comparison to lesions with an ISAR score of 0., Conclusions: This study developed and validated a risk prediction model for repeat PCI for recurrent DES-ISR at 1-year follow-up. This model served to generate the ISAR score, a standardised tool that can be used to predict the 1-year risk of repeat PCI for recurrent DES-ISR.

Background: The percutaneous treatment of severely calcified coronary lesions has been associated with lower performance of coronary stents and poor clinical long-term outcomes. Adequate lesion preparation before stent implantation is of paramount importance to minimize the risk of stent failure. Balloon-based techniques for lesion preparation have been the subject of numerous investigations, albeit comparative data from randomized trials are scarce., Study Design and Objectives: The ISAR-CALC 2 (ClinicalTrials.gov: NCT05072730) is an investigator-initiated, prospective, randomized, multicentre, assessors-blind, open-label trial designed to compare a lesion preparation strategy with either super high-pressure balloon or intravascular lithotripsy (IVL) before drug-eluting stent (DES) implantation in patients with severely calcified, undilatable coronary lesions. In total, 80 patients are required for trial completion. The primary endpoint will be final angiographic minimal lumen diameter (MLD) after stent implantation. Key secondary endpoints include stent expansion assessed by optical coherence tomography (OCT), procedural and strategy success, need for complementary lesion preparation with rotational atherectomy, acute lumen gain, and major adverse cardiac events up to 30-day follow-up., Conclusions: The ISAR-CALC 2 trial aims to demonstrate the superiority of a lesion preparation strategy with a super high-pressure balloon as compared with intravascular lithotripsy prior to DES implantation in patients with severely calcified undilatable coronary lesions., Competing Interests: Declaration of competing interest Dr. Rheude has received speaker fees from SIS Medical and AstraZeneca. Dr. Joner reports institutional grant support from Boston Scientific, Cardiac Dimensions, Edwards Lifesciences, and Infraredx; consulting fees from Biotronik, TriCares, Veryan, and Shockwave; speaker fees from Abbott, AstraZeneca, Biotronik, Boston Scientific, Cardiac Dimensions, Edwards Lifesciences, Recor Medical and Shockwave; participation on a Steering Committee of Biotronik and Edwards Lifesciences; travel support from Boston Scientific, Cardiac Dimensions, Edwards Lifesciences and SIS Medical. Dr. Abdel-Wahab reports that his hospital received speaker honoraria and/or consulting fees on his behalf from Medtronic and Boston Scientific. Dr. Cassese reports lecture/proctoring honoraria from SIS Medical, AstraZeneca, Boston Scientific, and Teleflex; and grants to the institution from SIS Medical, Boston Scientific, Abiomed, and Abbott Vascular. All other authors have no relevant conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background Several non-hyperemic pressure-derived Indexes (NHPI) have been introduced for the assessment of coronary stenosis, showing a good correlation with fractional flow reserve (FFR). Notably, either the assessment of NHPI during adenosine administration (NHPI ADO ) or the Hybrid Approach (NHPI HA ), combining NHPI with FFR, have been showed to increase the accuracy of such indexes. It remains unclear whether diagnostic performance might be affected by the extent of the subtended myocardial mass., Methods: We enrolled consecutive patients with an intermediate coronary stenosis assessed with NHPI and FFR. NHPI were also measured during adenosine (ADO) administration (NHPI ADO ). The amount of jeopardized myocardium was assessed using the Duke Jeopardy Score (DJS). With FFR as reference, we assessed the accuracy of NHPI, NHPI ADO and NHPI HA according to the extent of the subtended myocardium., Results: One-hundred-seventy stenoses from 151 patients were grouped according to the DJS as follows: A) Small Extent (SE, n = 82); B) Moderate Extent (ME, n = 53); C) Large Extent (LE, n = 35). As compared with FFR, NHPI showed a significantly different accuracy, as assessed by the Youden's index, according to the extent of the jeopardized myocardium (SE: 0.39 ± 0.05, ME: 0.68 ± 0.06, LE: 0.28 ± 0.06, p < 0.001). Conversely, both the NHPI ADO (SE: 0.76 ± 0.02, ME: 0.88 ± 0.02, LE: 0.82 ± 0.02, p = 0.72) and NHPI HA (SE: 0.82 ± 0.07, ME: 0.84 ± 0.02, LE: 0.88 ± 0.02, p = 0.70) allowed for a better diagnostic accuracy regardless of the amount of myocardium subtended., Conclusions: Diagnostic performance of NHPI might be affected by the extent of myocardial territory subtended by the coronary stenosis. A hybrid approach might be useful to overcome this limitation., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background The efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndrome and prior myocardial infarction (MI) remain unstudied. We aimed to assess the treatment effect of ticagrelor versus prasugrel according to prior MI status in patients with ACS. Methods and Results Patients with acute coronary syndrome planned for an invasive strategy and randomized to ticagrelor or prasugrel in the ISAR-REACT (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment) 5 trial were included. The primary end point was the composite of 1-year all-cause death, MI, or stroke; the secondary safety end point was the composite of 1-year Bleeding Academic Research Consortium type 3 to 5 bleeding. The study included 4015 patients (prior MI=631 patients; no prior MI=3384 patients). As compared with patients without prior MI, the primary end point occurred more frequently in patients with prior MI (12.6% versus 7.2%; hazard ratio [HR], 1.78 [95% CI, 1.38-2.29]); the secondary safety end point appears to differ little between patients with and without prior MI (5.8% versus 5.7%, respectively; HR, 1.02 [95% CI, 0.71-1.45]). With regard to the primary end point, ticagrelor versus prasugrel was associated with an HR of 1.62 (95% CI, 1.03-2.55) in patients with prior MI and an HR of 1.28 (95% CI, 0.99-1.65) in patients without prior MI ( P int =0.37). With regard to the secondary safety end point, ticagrelor versus prasugrel was associated with an HR of 1.28 (95% CI, 0.56-2.91) in patients with prior MI and an HR of 1.13 (95% CI, 0.82-1.55) in patients without prior MI ( P int =0.79). Conclusions Patients with acute coronary syndrome and prior MI are at higher risk for recurrent ischemic but not bleeding events. Prasugrel is superior to ticagrelor in reducing the risk of ischemic events without a tradeoff in bleeding regardless of prior MI status. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01944800.

The optimal antiplatelet therapy of patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and chronic kidney disease (CKD) remains unknown. This study included 2,364 patients with NSTE-ACS undergoing predominantly percutaneous coronary intervention (PCI), who were randomized to ticagrelor or prasugrel in the ISAR-REACT 5 trial. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. The primary end point was 1-year mortality. Overall, there were 85 deaths (3.6%): 6 deaths (17.1%) in patients with eGFR <30, 31 deaths (6.9%) in patients with eGFR 30 to <60, 34 deaths (3.0%) in patients with eGFR 60 to <90, and 14 deaths (2.0%) in patients with eGFR ≥90 ml/min/1.73 m 2 ; adjusted hazard ratio (HR)=1.15, 95% confidence interval (CI) 1.01 to 1.31; p = 0.033 for 10 ml/min/1.73 m 2 decrement in the eGFR. Bleeding occurred in 129 patients (5.5%): 7 bleeds (20.2%) in patients with eGFR <30, 36 bleeds (8.0%) in patients with eGFR 30 to <60, 64 bleeds (5.6%) in patients with eGFR 60 to <90, and 22 bleeds (3.1%) in patients with eGFR ≥90 ml/min/1.73 m 2 ; adjusted HR=1.11 (1.01 to 1.23); p = 0.045 for 10 ml/min/1.73 m 2 decrement in the eGFR. One-year mortality and bleeding did not differ significantly between ticagrelor and prasugrel in all categories of impaired renal function. In conclusion, in patients with NSTE-ACS undergoing PCI with drug-eluting stents and third-generation antiplatelet drugs, impaired renal function was independently associated with higher risk of 1-year mortality and bleeding. The ischemic and bleeding risks appear to differ little between ticagrelor and prasugrel in all categories of impaired renal function., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

(1) Aims: We sought to assess the impact of the extent of cardiac damage on survival among real-world patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). (2) Methods: A staging classification was applied to 262 patients from the EffecTAVI Registry at baseline and re-assessed within 30-days after TAVI. The primary endpoint of the study was all-cause mortality at 1-year. Secondary endpoints included cerebrovascular accident, myocardial infarction, permanent pacemaker implantation, endocarditis, and re-hospitalization for all causes. (3) Results: At baseline, 23 (8.7%) patients were in Stage 0/1 (no cardiac damage/left ventricular damage), 106 (40.4%) in Stage 2 (left atrial or mitral valve damage), 59 (22.5%) in Stage 3 (pulmonary vasculature or tricuspid valve damage) and 74 (28.3%) in Stage 4 (right ventricular damage). At 30-days after TAVI, a lower prevalence of advanced stages of cardiac damage than baseline, mainly driven by a significant improvement in left ventricular diastolic parameters and right ventricular function, was reported. At 1-year, a stepwise increase in mortality rates was observed according to staging at baseline: 4.3% in Stage 0/1, 6.6% in Stage 2, 18.6% in Stage 3 and 21.6% in Stage 4 ( p = 0.08). No differences were found in secondary endpoints. (4) Conclusions: TAVI has an early beneficial impact on the left ventricular diastolic and right ventricular function. However, the extent of cardiac damage at baseline significantly affects the risk of mortality at 1-year after the procedure.

Background: In 2016, an update of the 2009 recommendations for the evaluation of left ventricular (LV) diastolic function (DF) was released by the American Society of Echocardiography and the European Association of Cardiovascular Imaging. The aims of this study were to assess the concordance between the 2016 and 2009 recommendations and to test the impact of the consideration of "myocardial disease" recommended in the 2016 update on the evaluation of diastolic dysfunction (DD) and LV filling pressures in patients with normal and reduced LV ejection fractions referred to a general echocardiography laboratory., Methods: A total of 1,508 outpatients referred to an echocardiography laboratory during a predefined 5-month period were prospectively enrolled. All patients underwent targeted clinical history and Doppler echocardiographic examination. DD and LV filling pressures were assessed according to 2009 and 2016 recommendations. Concordance was calculated using the κ coefficient and overall proportion of agreement., Results: Overall proportion of agreement between the two recommendations was 64.7% (κ = 0.43). Comparing the 2009 and 2016 recommendations, 47.5% and 36.1% patients, respectively, had DD (P < .0001), and 22.7% and 12.6% had elevated LV filling pressures (P < .0001). This difference remained significant in the setting of patients with normal LV ejection fractions (21.6% vs 10.7%, P < .0001). In the application of the 2016 recommendations, whether or not the presence of "myocardial disease" was considered, the prevalence of indeterminate diastolic function was, respectively, 7.3% versus 13.7%, while patients in whom the DD grade could not be determined were 8.1% versus 14.4% (P < .0001 for all)., Conclusions: Considering the presence of myocardial disease when applying the 2016 recommendations resulted in a lower prevalence of inconclusive diagnosis., (Copyright © 2019 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)