Safety of metformin continuation in diabetic patients undergoing invasive coronary angiography: the NO-STOP single arm trial.

BACKGROUND: Despite paucity of data, it is common practice to discontinue metformin before invasive coronary angiography due to an alleged risk of Metformin-Associated Lactic Acidosis (M-ALA). We aimed at assessing the safety of metformin continuation in diabetic patients undergoing coronary angiography in terms of significant increase in lactate levels. METHODS: In this open-label, prospective, multicentre, single-arm trial, all diabetic patients undergoing coronary angiography with or without percutaneous coronary intervention at 3 European centers were screened for enrolment. The primary endpoint was the increase in lactate levels from preprocedural levels at 72-h after the procedure. Secondary endpoints included contrast associated-acute kidney injury (CA-AKI), M-ALA, and all-cause mortality. RESULTS: 142 diabetic patients on metformin therapy were included. Median preprocedural lactate level was 1.8 mmol/l [interquartile range (IQR) 1.3-2.3]. Lactate levels at 72 h after coronary angiography were 1.7 mmol/l (IQR 1.3-2.3), with no significant differences as compared to preprocedural levels (p = 0.91; median difference = 0; IQR - 0.5 to 0.4 mmol/l). One patient had 72-h levels ≥ 5 mmol/l (5.3 mmol/l), but no cases of M-ALA were reported. CA-AKI occurred in 9 patients (6.1%) and median serum creatinine and estimated glomerular filtration rate remained similar throughout the periprocedural period. At a median follow-up of 90 days (43-150), no patients required hemodialysis and 2 patients died due to non-cardiac causes. CONCLUSIONS: In diabetic patients undergoing invasive coronary angiography, metformin continuation throughout the periprocedural period does not increase lactate levels and was not associated with any decline in renal function. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov (NCT04766008).

Monotherapy with a P2Y12 inhibitor or aspirin for secondary prevention in patients with established atherosclerosis: a systematic review and meta-analysis.

BACKGROUND: Antiplatelet therapy is recommended among patients with established atherosclerosis. We compared monotherapy with a P2Y12 inhibitor versus aspirin for secondary prevention. METHODS: In this systematic review and meta-analysis, all randomised trials comparing P2Y12 inhibitor with aspirin monotherapy for secondary prevention in patients with cerebrovascular, coronary, or peripheral artery disease were evaluated for inclusion. On Dec 18, 2019, we searched PubMed, Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of Controlled Trials. Additionally, we reviewed references from identified articles and searched abstracts from 2017 to 2019 presented at relevant scientific meetings. Data about year of publication, inclusion and exclusion criteria, sample size, baseline patients' features including the baseline condition determining study inclusion (ie, cerebrovascular, coronary, or peripheral artery disease), P2Y12 inhibitor type and dosage, aspirin dosage, endpoint definitions, effect estimates, follow-up duration, and percentage of patients lost to follow-up were collected. Odds ratios (ORs) and 95% CIs were used as metric of choice for treatment effects with random-effects models. Co-primary endpoints were myocardial infarction and stroke. Key secondary endpoints were all-cause death and vascular death. Heterogeneity was assessed with the I2 index. This study is registered with PROSPERO (CRD42018115037). FINDINGS: A total of nine randomised trials were identified and included in this study, and 42 108 patients randomly allocated to a P2Y12 inhibitor (n=21 043) or aspirin (n=21 065) were included in our analyses. Patients who received a P2Y12 inhibitor had a borderline reduction for the risk of myocardial infarction compared with those who received aspirin (OR 0·81 [95% CI 0·66-0·99]; I2=10·9%). Risks of stroke (OR 0·93 [0·82-1·06]; I2=34·5%), all-cause death (OR 0·98 [0·89-1·08]; I2=0%), and vascular death (OR 0·97 [0·86-1·09]; I2=0%) did not differ between patients who received a P2Y12 inhibitor and those who received aspirin. Similarly, the risk of major bleeding (OR 0·90 [0·74-1·10]; I2=3·9%) did not differ between patients who received a P2Y12 inhibitor and those who received aspirin. The number needed to treat to prevent one myocardial infarction with P2Y12 inhibitor monotherapy was 244 patients. Findings were consistent regardless of the type of P2Y12 inhibitor used. INTERPRETATION: Compared with aspirin monotherapy, P2Y12 inhibitor monotherapy is associated with a risk reduction for myocardial infarction and a comparable risk of stroke in the setting of secondary prevention. The benefit of P2Y12 inhibitor monotherapy is of debatable clinical relevance, in view of the high number needed to treat to prevent a myocardial infarction and the absence of any effect on all-cause and vascular mortality. FUNDING: Italian Ministry of Education.

Drug-Coated balloons vs drug-eluting stents for the treatment of small coronary artery disease: A meta-analysis of randomized trials.

OBJECTIVES AND BACKGROUND: There is conflicting evidence about the effects of drug-coated balloons (DCB) compared with drug-eluting stents (DES) in patients with native small vessel coronary artery disease (CAD). METHODS: The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases and main international conference proceedings were searched for randomized controlled trials (RCT) comparing DCB versus DES in patients with native small vessel CAD. Data were pooled by meta-analysis using a random-effects model. The primary endpoint was target vessel revascularization (TVR). Secondary clinical endpoints were: myocardial infarction (MI), target lesion revascularization (TLR), all-cause death, cardiac death, and stent thrombosis or target vessel thrombosis. Secondary angiographic outcomes were: in-segment restenosis, in-segment percentage-diameter stenosis, in-segment late lumen loss, in-segment net luminal gain, and in-segment minimal lumen diameter. RESULTS: Five trials enrolling 1,459 patients were included. Mean clinical follow-up was 10.2 months. The use of DCB, compared with DES, was associated with similar risk of TVR (odds ratio [OR]: 0.97; 95% confidence interval [CI] 0.56 to 1.68; p = .92), TLR (OR: 1.74; 95% CI: 0.57 to 5.28; p = .33), all-cause death (OR: 1.03; 95% CI: 0.14 to 7.48; p = .98), with a trend toward a lower risk of MI (OR: 0.49; 95% CI: 0.23 to 1.03; p = .06), and with significant lower risk of vessel thrombosis (OR: 0.12; 95% CI: 0.01 to 0.94; p = .04). DCB use was associated with similar risk of angiographic restenosis (OR: 1.12; 95% CI 0.69 to 1.84; p = .64), comparable late luminal loss (standardized mean difference (SMD): -0.18; 95% CI: -0.39 to 0.03; p = .09), while leading to significant higher percentage diameter stenosis (SMD: 0.27; 95% CI 0.12 to 0.41; p < .01) and smaller minimal luminal diameter (SMD: -0.52; 95% CI: -0.86 to -0.18; p = .003). CONCLUSION: Compared with DES, the use of DCB for the treatment of native small vessel CAD is associated with similar TVR and restenosis and reduces the risk of vessel thrombosis, although DES implantation yields slightly better angiographic surrogate endpoints.

One-stop-shop totally percutaneous approach for severe aortic and mitral regurgitation in cardiogenic shock.

Patients presenting with cardiogenic shock and severe combined aortic and mitral regurgitation represent a major clinical challenge. Therapeutic options are limited in this setting as they are often deemed inoperable due to prohibitive risk for surgery, while mechanical circulatory support is usually contraindicated or technically challenging. Medical therapy, on the other hand, is associated with high-mortality rates. Therefore, percutaneous therapies may represent an appealing alternative. Here, we present a "one-stop-shop" totally percutaneous approach for severe aortic and mitral regurgitation in a patient with cardiogenic shock.

One-year clinical outcome of biodegradable polymer sirolimus-eluting stent in diabetic patients: Insight from the ULISSE registry (ULtimaster Italian multicenter all comerS Stent rEgistry).

BACKGROUND: The ULISSE registry evaluated the real-world performance of the Ultimaster® biodegradable polymer sirolimus-eluting stent (BP-SES) in a multicenter-independent cohort of patients undergoing percutaneous coronary intervention, including a large proportion of diabetes mellitus (DM) patients. METHODS: In this subgroup analysis, 1,660 consecutive patients, 2,422 lesions, treated with BP-SES enrolled in the ULISSE registry were divided in two groups: DM (485 patients, 728 lesions) and non-DM (1,175 patients, 1,694 lesions). Primary endpoint was target lesion failure (TLF), a composite endpoint of cardiac-death, target-vessel myocardial infarction (TV-MI), and clinically driven target lesion revascularization (TLR) at 1-year. Secondary endpoint was TLR at 1-year. RESULTS: At 1-year follow-up TLF occurred in 5% overall patients and was significantly higher in DM patients (8 vs. 3.7%; p = .001), due to more cardiac deaths (3.4 vs. 1.1%; p = .002). TLR occurred in 3.2% overall patients, and it was not significantly higher in DM compared to non-DM patients (4.4 vs. 2.8%; p = .114). The incidence of stent thrombosis was low and similar between groups (0.4 vs. 0.9%; p = .526). Insulin-treated DM (ITDM) patients showed higher rate of TLF as compared to non-ITDM patients (13 vs. 6.5%; p = .041), but similar rate of TLR (6 vs. 4%; p = .405). After adjustment for relevant comorbidities, DM was not significantly associated with TLF or cardiac death in patients undergoing BP-SES implantation. CONCLUSIONS: This study is the first all-comers evaluation of BP-SES in DM patients. Our findings show that DM patients, mostly those with ITDM, still represent a vulnerable population and experience significantly higher rate of TLF. Overall BP-SES efficacy is considerable, although not statistically significant higher rate of TLR is still present in DM compared to non-DM patients.

Radial versus femoral access and bivalirudin versus unfractionated heparin in invasively managed patients with acute coronary syndrome (MATRIX): final 1-year results of a multicentre, randomised controlled trial.

BACKGROUND: The Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox (MATRIX) programme was designed to assess the comparative safety and effectiveness of radial versus femoral access and of bivalirudin versus unfractionated heparin with optional glycoprotein IIb/IIIa inhibitors in patients with the whole spectrum of acute coronary syndrome undergoing invasive management. Here we describe the prespecified final 1-year outcomes of the entire programme. METHODS: MATRIX was a programme of three nested, randomised, multicentre, open-label, superiority trials in patients with acute coronary syndrome in 78 hospitals in Italy, the Netherlands, Spain, and Sweden. Patients with ST-elevation myocardial infarction were simultaneously randomly assigned (1:1) before coronary angiography to radial or femoral access and to bivalirudin, with or without post-percutaneous coronary intervention infusion or unfractionated heparin (one-step inclusion). Patients with non-ST-elevation acute coronary syndrome were randomly assigned (1:1) before coronary angiography to radial or femoral access and, only if deemed eligible to percutaneous coronary intervention after angiography (two-step inclusion), entered the antithrombin type and treatment duration programmes. Randomisation sequences were computer generated, blocked, and stratified by intended new or current use of P2Y12 inhibitor (clopidogrel vs ticagrelor or prasugrel), and acute coronary syndrome type (ST-elevation myocardial infarction, troponin-positive, or troponin-negative non-ST-elevation acute coronary syndrome). Bivalirudin was given as a bolus of 0·75 mg/kg, followed immediately by an infusion of 1·75 mg/kg per h until completion of percutaneous coronary intervention. Heparin was given at 70-100 units per kg in patients not receiving glycoprotein IIb/IIIa inhibitors, and at 50-70 units per kg in patients receiving glycoprotein IIb/IIIa inhibitors. Clinical follow-up was done at 30 days and 1 year. Co-primary outcomes for MATRIX access and MATRIX antithrombin type were major adverse cardiovascular events, defined as the composite of all-cause mortality, myocardial infarction, or stroke up to 30 days; and net adverse clinical events, defined as the composite of non-coronary artery bypass graft-related major bleeding, or major adverse cardiovascular events up to 30 days. The primary outcome for MATRIX treatment duration was the composite of urgent target vessel revascularisation, definite stent thrombosis, or net adverse clinical events up to 30 days. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01433627. FINDINGS: Between Oct 11, 2011, and Nov 7, 2014, we randomly assigned 8404 patients to receive radial (4197 patients) or femoral (4207 patients) access. Of these 8404 patients, 7213 were included in the MATRIX antithrombin type study and were randomly assigned to bivalirudin (3610 patients) or heparin (3603 patients). Patients assigned to bivalirudin were included in the MATRIX treatment duration study, and were randomly assigned to post-procedure infusion (1799 patients) or no post-procedure infusion (1811 patients). At 1 year, major adverse cardiovascular events did not differ between patients assigned to radial access compared with those assigned to femoral access (14·2% vs 15·7%; rate ratio 0·89, 95% CI 0·80-1·00; p=0·0526), but net adverse clinical events were fewer with radial than with femoral access (15·2% vs 17·2%; 0·87, 0·78-0·97; p=0·0128). Compared with heparin, bivalirudin was not associated with fewer major adverse cardiovascular (15·8% vs 16·8%; 0·94, 0·83-1·05; p=0·28) or net adverse clinical events (17·0% vs 18·4%; 0·91, 0·81-1·02; p=0·10). The composite of urgent target vessel revascularisation, stent thrombosis, or net adverse clinical events did not differ with or without post-procedure bivalirudin infusion (17·4% vs 17·4%; 0·99, 0·84-1·16; p=0·90). INTERPRETATION: In patients with acute coronary syndrome, radial access was associated with lower rates of net adverse clinical events compared with femoral access, but not major adverse cardiovascular events at 1 year. Bivalirudin with or without post-procedure infusion was not associated with lower rates of major adverse cardiovascular events or net adverse clinical events. Radial access should become the default approach in acute coronary syndrome patients undergoing invasive management. FUNDING: Italian Society of Invasive Cardiology, The Medicines Company, Terumo, amd Canada Research Chairs Programme.

One-year clinical outcome of biodegradable polymer sirolimus-eluting stent in patients presenting with acute myocardial infarction: Insight from the ULISSE registry.

BACKGROUND: The ULISSE registry has demonstrated the real-world performance of the Ultimaster biodegradable polymer sirolimus-eluting stent (BP-SES) in a large cohort of patients undergoing percutaneous coronary intervention, including a large proportion of patients presenting with acute myocardial infarction (AMI). METHODS: We performed a subgroup analysis of the ULISSE registry in AMI patients and compared the outcomes of this vulnerable cohort with that of patients presenting without AMI (non-AMI). The primary end point was the incidence of 1-year target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (TV-MI), and clinically indicated target lesion revascularization (TLR). RESULTS: Of 1,660 patients included in the ULISSE registry, 381(23%) presented with AMI, 207(54.3%) non-ST elevation myocardial infarction, and 174(45.7%) ST-elevation myocardial infarction. Compared with non-AMI patients, those with AMI were more frequently female and smokers, with lower left ventricular ejection fraction (LVEF) and chronic kidney disease requiring dialysis. At 1 year, TLF rate was significantly higher in AMI than non-AMI patients (7.9 vs. 4.1%; HR 1.98, CI 95% 1.22-3.23; p = .005) driven by higher rate of cardiac death (4.0 vs. 1.1%; HR 3.59, CI 95% 1.64-7.88; p = .01) and TV-MI (2.8 vs 0.9%; HR 2.99,CI 95% 1.22-7.37; p = .01), without differences in TLR rate (4.3 vs. 2.9%,HR 0.66, CI95% 0.35-1.25; p = .2). At multivariate Cox regression analysis, eGFR <40 mL/min (HR: 2.868) and LVEF <40% (HR: 2.394) were the only independent predictors of TLF. CONCLUSIONS: In AMI patients, Ultimaster BP-SES implantation was associated with higher rate of TLF and definite stent thrombosis compared with non-AMI patients. The high incidence of adverse events was mainly driven by the unfavorable baseline risk profile.

Cost-effectiveness of percutaneous coronary intervention with cobalt-chromium everolimus eluting stents versus bare metal stents: Results from a patient level meta-analysis of randomized trials.

BACKGROUND: Second-generation drug eluting stents (DES) may reduce costs and improve clinical outcomes compared to first-generation DES with improved cost-effectiveness when compared to bare metal stents (BMS). We aimed to conduct an economic evaluation of a cobalt-chromium everolimus eluting stent (Co-Cr EES) compared with BMS in percutaneous coronary intervention (PCI). OBJECTIVE: To conduct a cost-effectiveness analysis (CEA) of a cobalt-chromium everolimus eluting stent (Co-Cr EES) versus BMS in PCI. METHODS: A Markov state transition model with a 2-year time horizon was applied from a US Medicare setting with patients undergoing PCI with Co-Cr EES or BMS. Baseline characteristics, treatment effects, and safety measures were taken from a patient level meta-analysis of 5 RCTs (n = 4,896). The base-case analysis evaluated stent-related outcomes; a secondary analysis considered the broader set of outcomes reported in the meta-analysis. RESULTS: The base-case and secondary analyses reported an additional 0.018 and 0.013 quality-adjusted life years (QALYs) and cost savings of $236 and $288, respectively with Co-Cr EES versus BMS. Results were robust to sensitivity analyses and were most sensitive to the price of clopidogrel. In the probabilistic sensitivity analysis, Co-Cr EES was associated with a greater than 99% chance of being cost saving or cost effective (at a cost per QALY threshold of $50,000) versus BMS. CONCLUSIONS: Using data from a recent patient level meta-analysis and contemporary cost data, this analysis found that PCI with Co-Cr EES is more effective and less costly than PCI with BMS. © 2016 The Authors. Catheterization and Cardiovascular Interventions Published by Wiley Periodicals, Inc.

Bivalirudin versus heparin in patients with acute myocardial infarction: A meta-analysis of randomized trials.

BACKGROUND: The aim of this study was to assess the impact of bivalirudin, as compared to unfractionated heparin, on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: A meta-analysis of randomized trials comparing bivalirudin versus heparin in patients with STEMI undergoing primary percutaneous coronary intervention was performed. Three randomised trials enrolling 7,612 patients were included. Analysis was by intention to treat. RESULTS: At 30 days, bivalirudin, as compared to heparin, was associated with a similar risk of all-cause mortality (3.03% vs. 3.38%, odds ratio (OR) 0.90, 95% confidence intervals (CI) [0.63 to 1.29], P = 0.57). Bivalirudin significantly increased the risk of definite (2.39% vs. 1.06%, OR 2.49, 95% CI [1.30 to 4.76], P = 0.006); definite or probable (2.55% vs. 1.35%, OR 2.26, 95% CI [1.07 to 4.79], P = 0.03), and acute stent thrombosis (1.69% vs. 0.39%, OR 4.34, 95% CI [2.30 to 8.16], P < 0.001); leading to nonsignificantly higher reinfarction rates (2.0% vs. 1.31%, OR 1.72, 95% CI [0.89 to 3.35], P = 0.11), and to a significantly increased risk of ischemia driven revascularization (2.50% vs. 1.52%, OR 1.80, 95% CI [1.02 to 3.18], P = 0.04) at 30 days. No firm evidence for a reduction in major bleeding associated with bivalirudin use was found (3.93% vs. 6.39%, OR 0.63, 95% CI [0.39 to 1.04], P = 0.07). CONCLUSIONS: In patients with STEMI, bivalirudin, as compared to heparin, increases the risk of stent thrombosis and ischemia driven repeat revascularization at 30 days. There is no strong evidence that bivalirudin significantly reduces major bleeding at 30 days. Bivalirudin does not have an effect on all-cause mortality at 30 days.

Rescue "valve in valve" implantation after late onset CoreValve cusp rupture leading to acute massive aortic insufficiency.

Transcatheter aortic valve implantation (TAVI) has emerged as a feasible and effective alternative to aortic valve replacement in patients at high surgical risk, and is associated with a lower risk of death at 1 year follow-up when compared with standard therapy. In a recent large study, enrolling 663 high risk patients with symptomatic severe aortic stenosis TAVI with the use of CoreValve system has been associated with early and sustained clinical and hemodynamic benefits, with a cumulative mortality of 15.0% at 1 year follow-up. This study has shown that paravalvular aortic regurgitation after successful TAVI is a frequent finding, being of mild entity in the vast majority of cases, whereas valvular regurgitation is almost entirely absent or mild. Of note, no cases of structural valve deterioration were reported. We report a case of a successful implantation of a CoreValve that complicated with late onset massive intravalvular aortic regurgitation, due to CoreValve cusp rupture, leading to low output state with acute pulmonary edema, which was successfully treated with "valve in valve" implantation.

Sex differences in postprocedural aortic regurgitation and mid-term mortality after transcatheter aortic valve implantation.

BACKGROUND: The impact of female sex on mortality after transcatheter aortic valve implantation (TAVI) is controversial. Post-procedural aortic regurgitation (AR) ≥ 2 has been associated with poor outcomes. Whether sex differences in post-procedural AR ≥ 2 could contribute to a mortality difference between women and men is not known. METHODS: Six hundred fifty-six patients, women (53.1%), men (46.9%), with aortic stenosis underwent TAVI with the CoreValve system (92.8%) or the Edwards SAPIEN valve system (7.2%). AR was graded semiquantitatively as 0 = none, 1 = trivial, 2 = mild, 3 = moderate, and 4 = severe. The incidence of post-procedural AR ≥ 2 was reported. RESULTS: Procedural success was similar in women as compared to men (97.9 vs 96.7%, P = 0.32). Post-procedural AR ≥ 2 occurred less frequently in women than in men (20.9 vs 29.6%, P = 0.01). After a median follow-up of 434 days, all-cause mortality tended to be lower in women than in men (20.7 vs 26.6%, logrank P = 0.10), and was significantly higher in patients with AR ≥ 2 than in those without (34.8 vs 19.7%, logrank P < 0.001). AR ≥ 2 [hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.22-2.43, P = 0.002], but not female sex (P = 0.17) was an independent predictor of all-cause death at multivariable Cox regression. The predictive value of AR ≥ 2 was restricted to men (HR 2.96, P < 0.001 among men; HR 0.86, P = 0.60 among women; P for interaction = 0.002). CONCLUSIONS: Women, as compared to men, present a trend toward lower mortality. A significant lower incidence of post-procedural AR ≥ 2 among women contributes to this finding. Female sex, however, was not a significant independent predictor of death.

GLP-1-ra and heart failure-related outcomes in patients with and without history of heart failure: an updated systematic review and meta-analysis.

AIMS: Glucagon-like peptide-1 receptor agonists (GLP1-ra) have shown to reduce cardiovascular (CV) events in patients with diabetes, including heart failure (HF) hospitalizations. However, whether such benefit consistently occurs in patients with history of HF remains uncertain. We performed a systematic review and meta-analysis to assess the impact of GLP1-ra on CV outcomes in patients with and without HF history. METHODS AND RESULTS: All randomized, placebo-controlled trials evaluating GLP1-ra and reporting CV outcomes stratified by HF history were searched in Pubmed from inception to November 12th, 2023. The primary outcome was HF hospitalizations. Secondary outcomes included CV death, the composite of CV death and hospitalizations for HF, and major adverse cardiovascular events (MACE). Hazard ratio (HR) and 95% confidence interval (CIs) were used as effect estimates and calculated with a random-effects model. 68,653 patients (GLP1-ra = 34,301, placebo = 34,352) from 10 trials were included. GLP1-ra reduced HF hospitalization (no HF: HR = 0.79, 95% CI 0.63-0.98; HF: HR = 1.00, 95% CI 0.82-1.24, pinteraction = 0.12), CV death (no HF: HR = 0.81, 95% CI 0.71-0.92; HF: HR = 0.97, 95% CI 0.81-1.15, pinteraction = 0.11), and the composite of HF hospitalizations and CV death (no HF: HR = 0.80, 95% CI 0.72-0.89; HF: HR = 1.00 95% CI 0.88-1.15, pinteraction = 0.010) only in patients without history of HF, despite a significant interaction between HF history and treatment effect was detected only for the latter. MACE were reduced in both subgroups without significant interaction between HF history and treatment effect (no HF: HR = 0.86, 95% CI 0.78-0.96; HF: HR = 0.83, 95% CI 0.72-0.95, pinteraction = 0.69). CONCLUSION: GLP1-ra do not decrease HF-hospitalization risk, despite a potential benefit in patients without history of HF, but are effective in reducing ischemic events irrespective of the presence of HF. PROSPERO-registered (CRD42022371264).

The Smokers Health Multiple ACtions (SMAC-1) Trial: Study Design and Results of the Baseline Round.

BACKGROUND: Lung cancer screening with low-dose helical computed tomography (LDCT) reduces mortality in high-risk subjects. Cigarette smoking is linked to up to 90% of lung cancer deaths. Even more so, it is a key risk factor for many other cancers and cardiovascular and pulmonary diseases. The Smokers health Multiple ACtions (SMAC-1) trial aimed to demonstrate the feasibility and effectiveness of an integrated program based on the early detection of smoking-related thoraco-cardiovascular diseases in high-risk subjects, combined with primary prevention. A new multi-component screening design was utilized to strengthen the framework on conventional lung cancer screening programs. We report here the study design and the results from our baseline round, focusing on oncological findings. METHODS: High-risk subjects were defined as being >55 years of age and active smokers or formers who had quit within 15 years (>30 pack/y). A PLCOm2012 threshold >2% was chosen. Subject outreach was streamlined through media campaign and general practitioners' engagement. Eligible subjects, upon written informed consent, underwent a psychology consultation, blood sample collection, self-evaluation questionnaire, spirometry, and LDCT scan. Blood samples were analyzed for pentraxin-3 protein levels, interleukins, microRNA, and circulating tumor cells. Cardiovascular risk assessment and coronary artery calcium (CAC) scoring were performed. Direct and indirect costs were analyzed focusing on the incremental cost-effectiveness ratio per quality-adjusted life years gained in different scenarios. Personalized screening time-intervals were determined using the "Maisonneuve risk re-calculation model", and a threshold <0.6% was chosen for the biennial round. RESULTS: In total, 3228 subjects were willing to be enrolled. Out of 1654 eligible subjects, 1112 participated. The mean age was 64 years (M/F 62/38%), with a mean PLCOm2012 of 5.6%. Former and active smokers represented 23% and 77% of the subjects, respectively. At least one nodule was identified in 348 subjects. LDCTs showed no clinically significant findings in 762 subjects (69%); thus, they were referred for annual/biennial LDCTs based on the Maisonneuve risk (mean value = 0.44%). Lung nodule active surveillance was indicated for 122 subjects (11%). Forty-four subjects with baseline suspicious nodules underwent a PET-FDG and twenty-seven a CT-guided lung biopsy. Finally, a total of 32 cancers were diagnosed, of which 30 were lung cancers (2.7%) and 2 were extrapulmonary cancers (malignant pleural mesothelioma and thymoma). Finally, 25 subjects underwent lung surgery (2.25%). Importantly, there were zero false positives and two false negatives with CT-guided biopsy, of which the patients were operated on with no stage shift. The final pathology included lung adenocarcinomas (69%), squamous cell carcinomas (10%), and others (21%). Pathological staging showed 14 stage I (47%) and 16 stage II-IV (53%) cancers. CONCLUSIONS: LDCTs continue to confirm their efficacy in safely detecting early-stage lung cancer in high-risk subjects, with a negligible risk of false-positive results. Re-calculating the risk of developing lung cancer after baseline LDCTs with the Maisonneuve model allows us to optimize time intervals to subsequent screening. The Smokers health Multiple ACtions (SMAC-1) trial offers solid support for policy assessments by policymakers. We trust that this will help in developing guidelines for the large-scale implementation of lung cancer screening, paving the way for better outcomes for lung cancer patients.

Immediate results of bifurcational stenting assessed with optical coherence tomography.

BACKGROUND: A tubular stent may adapt with difficulty to coronary bifurcation lesions (CBLs). METHODS: Time domain or frequency domain (FD) optical coherence tomography (OCT) was performed to assess strut apposition immediately after stent implantation across four segments inside the bifurcation, in a consecutive series of patients. OCT pullbacks were performed in the main vessel (MV). RESULTS: A total of 13,142 struts in 45 CBL in 41 patients were assessed. Strut malapposition was significantly more frequent in the half bifurcation facing the side-branch (SB) ostium (42.9%) than in the proximal segment of the bifurcation 11.8%, half bifurcation opposite the SB 6.7%, or the distal segment 5.7% (all P < 0.0001). Lesions (n = 15) treated with stenting of both MV and SB had a total higher rate of malapposition than those (n = 30) treated with stenting of the MV only (17.6% vs. 9.5%; P = 0.0014). In latter group, lesions treated with FD-OCT-guided stent implantation (n = 13) presented a lower rate of malapposition than those treated with conventional angiographic-guided stent implantation (n = 17) (7.1% vs. 17.5%; P = 0.005). CONCLUSIONS: In CBL, strut malapposition is particularly high at the SB ostium. However, a strategy of stenting MV only with adjunctive FD-OCT guidance is associated with lower rates of malapposition.

Validation of a Contemporary Acute Kidney Injury Risk Score in Patients With Acute Coronary Syndrome.

BACKGROUND: A simple, contemporary risk score for the prediction of contrast-associated acute kidney injury (CA-AKI) after percutaneous coronary intervention (PCI) was recently updated, although its external validation is lacking. OBJECTIVES: The aim of this study was to validate the updated CA-AKI risk score in a large cohort of acute coronary syndrome patients from the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of angioX) trial. METHODS: The risk score identifies 4 risk categories for CA-AKI. The primary endpoint was to appraise the receiver-operating characteristics of an 8-component and a 12-component CA-AKI model. Independent predictors of Kidney Disease Improving Global Outcomes-based acute kidney injury and the impact of CA-AKI on 1-year mortality and bleeding were also investigated. RESULTS: The MATRIX trial included 8,201 patients with complete creatinine values and no end-stage renal disease. CA-AKI occurred in 5.5% of the patients, with a stepwise increase of CA-AKI rates from the lowest to the highest of the 4 risk categories. The receiver-operating characteristic area under the curve was 0.67 (95% CI: 0.64-0.70) with model 1 and 0.71 (95% CI: 0.68-0.74) with model 2. CA-AKI risk was systematically overestimated with both models (Hosmer-Lemeshow goodness-of-fit test: P < 0.05). The 1-year risks of all-cause mortality and bleeding were higher in CA-AKI patients (HR: 7.03 [95% CI: 5.47-9.05] and HR: 3.20 [95% CI: 2.56-3.99]; respectively). There was a gradual risk increase for mortality and bleeding as a function of the CA-AKI risk category for both models. CONCLUSIONS: The updated CA-AKI risk score identifies patients at incremental risks of acute kidney injury, bleeding, and mortality. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of angioX [MATRIX]; NCT01433627).

Nebivolol versus placebo in patients undergoing anthracyclines (CONTROL Trial): rationale and study design.

AIMS: Anthracyclines are the chemotherapeutic agents most frequently associated with cardiotoxicity, while remaining widely used. Different neurohormonal blockers have been tested as a primary prevention strategy to prevent or attenuate the onset of cardiotoxicity, with mixed results. However, prior studies were often limited by a nonblinded design and an assessment of cardiac function based only on echocardiographic imaging. Moreover, on the basis of an improved mechanistic understanding of anthracycline cardiotoxicity mechanisms, new therapeutic strategies have been proposed. Among cardioprotective drugs, nebivolol might be able to prevent the cardiotoxic effects of anthracyclines, through its protective properties towards the myocardium, endothelium, and cardiac mitochondria. This study aims to evaluate the cardioprotective effects of the beta blocker nebivolol in a prospective, placebo-controlled, superiority randomized trial in patients with breast cancer or diffuse large B cell lymphoma (DLBCL) who have a normal cardiac function and will receive anthracyclines as part of their first-line chemotherapy programme. METHODS: The CONTROL trial is a randomized, placebo-controlled, double-blinded, superiority trial. Patients with breast cancer or a DLBCL, with a normal cardiac function as assessed by echocardiography, scheduled for treatment with anthracyclines as part of their first-line chemotherapy programme will be randomized 1 : 1 to nebivolol 5 mg once daily (o.d.) or placebo. Patients will be examined with cardiological assessment, echocardiography and cardiac biomarkers at baseline, 1 month, 6 months and 12 months. A cardiac magnetic resonance (CMR) assessment will be performed at baseline and at 12 months. The primary end point is defined as left ventricular ejection fraction reduction assessed by CMR at 12 months of follow-up. CONCLUSION: The CONTROL trial is designed to provide evidence to assess the cardioprotective role of nebivolol in patients undergoing chemotherapy with anthracyclines. CLINICAL TRIAL REGISTRATION: The study is registered in the EudraCT registry (number: 2017-004618-24) and in the ClinicalTrials.gov registry (identifier: NCT05728632).

Rationale and design of the CV-PREVITAL study: an Italian multiple cohort randomised controlled trial investigating innovative digital strategies in primary cardiovascular prevention.

INTRODUCTION: Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking. METHODS AND ANALYSIS: The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners' offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed. ETHICS AND DISSEMINATION: This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study's course and findings through regular meetings. TRIAL REGISTRATION NUMBER: NCT05339841.