Cataldo Palmieri

Radial versus femoral access in patients with acute coronary syndromes undergoing invasive management: a randomised multicentre trial

BACKGROUND It is unclear whether radial compared with femoral access improves outcomes in unselected patients with acute coronary syndromes undergoing invasive management. METHODS We did a randomised, multicentre, superiority trial comparing transradial against transfemoral access in patients with acute coronary syndrome with or without ST-segment elevation myocardial infarction who were about to undergo coronary angiography and percutaneous coronary intervention. Patients were randomly allocated (1:1) to radial or femoral access with a web-based system. The randomisation sequence was computer generated, blocked, and stratified by use of ticagrelor or prasugrel, type of acute coronary syndrome (ST-segment elevation myocardial infarction, troponin positive or negative, non-ST-segment elevation acute coronary syndrome), and anticipated use of immediate percutaneous coronary intervention. Outcome assessors were masked to treatment allocation. The 30-day coprimary outcomes were major adverse cardiovascular events, defined as death, myocardial infarction, or stroke, and net adverse clinical events, defined as major adverse cardiovascular events or Bleeding Academic Research Consortium (BARC) major bleeding unrelated to coronary artery bypass graft surgery. The analysis was by intention to treat. The two-sided α was prespecified at 0·025. The trial is registered at ClinicalTrials.gov, number NCT01433627. FINDINGS We randomly assigned 8404 patients with acute coronary syndrome, with or without ST-segment elevation, to radial (4197) or femoral (4207) access for coronary angiography and percutaneous coronary intervention. 369 (8·8%) patients with radial access had major adverse cardiovascular events, compared with 429 (10·3%) patients with femoral access (rate ratio [RR] 0·85, 95% CI 0·74-0·99; p=0·0307), non-significant at α of 0·025. 410 (9·8%) patients with radial access had net adverse clinical events compared with 486 (11·7%) patients with femoral access (0·83, 95% CI 0·73-0·96; p=0·0092). The difference was driven by BARC major bleeding unrelated to coronary artery bypass graft surgery (1·6% vs 2·3%, RR 0·67, 95% CI 0·49-0·92; p=0·013) and all-cause mortality (1·6% vs 2·2%, RR 0·72, 95% CI 0·53-0·99; p=0·045). INTERPRETATION In patients with acute coronary syndrome undergoing invasive management, radial as compared with femoral access reduces net adverse clinical events, through a reduction in major bleeding and all-cause mortality. FUNDING The Medicines Company and Terumo.

The atropine factor in pharmacologic stress echocardiography

Objectives. This study sought to compare, head to head, the two most popular pharmacologic stress echocardiographic tests-dipyridamole and dobutamin-with state of the art protocols in a large multicenter prospective study. Background. In the continuing quest for ideal diagnostic accuracy, pharmacologic stress echocardiography has quickly moved over the years from low to high dose regimens and is currently performed with atropine coadministration. Methods. Dobutamine (up to 40 μg/kg body weight per min) plus atropine (up to 1 mg over 4 h) and dipyridamole (up to 0.84 mg/kg per min over 10 h) plus atropine (up to 1 mg over 4 h) stress echocardiography was performed on different days, in random order and within 1 week in 360 patients with chest pain syndrome. Thirteen different echocardiographic laboratories, all fulfilling quality control criteria for stress echocardiographic reading, contributed to the study. Results. No major complications occurred during either test. The test was interrupted before achievement of predetermined end points for limiting side effects in 37 dobutamine-atropine and 7 dipyridamole-atropine stress echocardiographic studies (feasibility 90% vs. 98%, p < 0.01). Diagnostic accuracy was assessed in a subset of 110 patients with no obvious rest dyssynergy (akinesia or dyskinesia) who underwent coronary angiography independently of test results and within 1 week of testing. Significant coronary artery disease (≥50% diameter reduction in at least one major coronary vessel by quantitative coronary angiography) was found in 92 patients. Sensitivity for detection of coronary artery disease was 84% (77 of 92) for dobutamine-atropine and 82% (75 of 92) for dipyridamole-atropine stress echocardiography (p = NS), with a specificity of 89% (16 of 18) for dobutamine-atropine and 94% (17 of 18) for dipyridamole-atropine stress echocardiography (p = NS). A significant correlation was present between peak wall motion score index during dipyridamole-atropine and dobutamine-atropine stress echocardiography (r = 0.83, p < 0.0001). Conclusions. Dobutamine-atropine and dipyridamole-atropine stress echocardiography are safe and feasible, although submaximal studies are more frequent with dobutamine. The two stresses have comparable accuracy in the detection of angiographically assessed coronary artery disease, although dobutamine is marginally more sensitive and dipyridamole marginally more specific. Stratification of the ischemic response in the space domain is also comparable with the two stresses.

Ostial and midshaft lesions vs. bifurcation lesions in 1111 patients with unprotected left main coronary artery stenosis treated with drug-eluting stents: results of the survey from the Italian Society of Invasive Cardiology

AIMS In this study, we compared the cumulative risk of major adverse cardiac events (MACE) of patients with distal unprotected left main coronary artery (ULMCA) stenosis with those of patients with ostial and midshaft lesions treated with drug-eluting stent (DES). METHODS AND RESULTS The survey promoted by the Italian Society of Invasive Cardiology on ULMCA stenosis was an observational study involving 19 high-volume Italian centres. We enrolled 1111 patients with ULMCA stenosis treated with DES. Major adverse cardiac events were defined as death, myocardial infarction, and target lesion revascularization. Three hundred and thirty-four patients had ostial or midshaft lesions (group 1) and 777 bifurcations (group 2). The adjusted hazards ratio of the risk of 2 year MACE of patients in group 2 vs. patients in group 1 was 1.50 (P = 0.024). However, we observed that there was a significant difference between patients with bifurcations treated with two stents and those in group 1 (P = 0.001), but not between patients with bifurcations treated with one stent and those in group 1 (P = 0.38). CONCLUSION Patients with bifurcations have a worse outcome than patients with ostial and midshaft lesions. However, the technique used to treat bifurcations has a significant impact on clinical outcomes.

Impact of Bifurcation Technique on 2-Year Clinical Outcomes in 773 Patients With Distal Unprotected Left Main Coronary Artery Stenosis Treated With Drug-Eluting Stents

Background—Distal unprotected left main coronary artery (ULMCA) stenosis represents a technical challenge for interventional cardiologists. In this study, we compared 2-year clinical outcomes of different stenting strategies in patients with distal ULMCA stenosis treated with drug-eluting stents. Methods and Results—The survey promoted by the Italian Society of Invasive Cardiology on ULMCA stenosis was an observational study on patients with ULMCA stenosis treated with percutaneous coronary intervention. In this study, we selected patients with distal ULMCA stenosis treated with drug-eluting stents. Seven hundred seventy-three patients were eligible for this study: 456 were treated with 1 stent (group 1) and 317 with 2 stents (group 2). The primary end point of the study was the incidence of major adverse cardiac events (MACEs), defined as the occurrence of mortality, myocardial infarction, and target lesion revascularization. During a 2-year follow-up, risk-adjusted survival free from MACE was significantly higher in patients in group 1 than in patients in group 2. The propensity-adjusted hazard ratio for the risk of 2-year MACE in patients in group 1 versus group 2 was 0.53 (95% CI, 0.37 to 0.76). The propensity-adjusted hazard ratio for the risk of 2-year cardiac mortality and myocardial infarction in patients in group 1 versus group 2 was 0.38 (95% CI, 0.17 to 0.85). Conclusions—Compared with the 2-stent technique, the 1-stent technique is associated with a better 2-year MACE-free survival. The stenting strategy is a prognostic factor that should be taken into account when deciding the optimal revascularization treatment.

Long-term invasive follow-up of the everolimus-eluting bioresorbable vascular scaffold: Five-year results of multiple invasive imaging modalities

AIMS Invasive imaging modalities have shown restoration of vasomotion, prevention of restenosis and, most importantly, increase in lumen area between six months and two years after first-generation everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) implantation. Our aim was to assess whether these positive findings were sustained in the long term. METHODS AND RESULTS Patients included in the ABSORB cohort A from the Thoraxcenter Rotterdam cohort underwent coronary catheterisation including angiography, intravascular ultrasound (IVUS), virtual histology, optical coherence tomography (OCT) and vasomotion testing at five years. Eight out of 16 patients underwent catheterisation and scaffold assessment with multiple imaging modalities. A trend towards an increase in minimum luminal diameter was observed between two and five years by angiography (1.95±0.37 mm vs. 2.14±0.38 mm; p=0.09). IVUS data showed an increase in mean lumen area at five years (6.96±1.13 mm2) compared to six months (6.17±0.74 mm2; p=0.06) and two years (6.56±1.16 mm2; p=0.12), primarily due to a persistent reduction in plaque area size between six months and five years (9.17±1.86 mm2 vs. 7.57±1.63 mm2; p=0.03). The necrotic core area was reduced at five years compared to post-procedural results. In OCT, an increase in mean and minimal luminal area was observed. Moreover, no scaffold struts could be identified and a smooth endoluminal lining was observed. The scaffolded coronary segment did not show signs of endothelial dysfunction with acetylcholine testing. CONCLUSIONS At five years, the Absorb BVS is no longer discernible by any invasive imaging method and endothelial function is restored. Late luminal enlargement persists up to five years of follow-up without adaptive vessel remodelling.

Up-regulation of ‘clearance’ receptors in patients with chronic heart failure: a possible explanation for the resistance to biological effects of cardiac natriuretic hormones

Three specific receptors for the cardiac natriuretic peptide system have been identified to date. Down‐regulation of the biologically active binding sites (i.e. NPR‐A and NPR‐B) could explain the blunted response to cardiac natriuretic hormones observed in heart failure (HF), but not the increased metabolic clearance rate. Variations in the ratio between biological and clearance (NPR‐C) receptors in target tissue may explain this increase.

Two-Year Clinical Outcome With Drug-Eluting Stents Versus Bare-Metal Stents in a Real-World Registry of Unprotected Left Main Coronary Artery Stenosis from the Italian Society of Invasive Cardiology

Data are limited about the relative efficacy of drug-eluting stents (DESs) versus bare-metal stents (BMSs) for the treatment of unprotected left main coronary artery (ULMCA) stenosis. The survey promoted by the Italian Society of Invasive Cardiology on ULMCA stenosis was an observational study involving 19 high-volume Italian centers of patients with ULMCA stenosis treated using percutaneous coronary intervention (PCI). From January 2002 to December 2006, of 1,453 patients identified with ULMCA stenosis treated with PCI, 1,111 were treated with DESs and 342 were treated with BMSs. During a 2-year follow-up, risk-adjusted survival free from cardiac death was significantly higher in patients treated with DESs than in those treated with BMSs. The propensity-adjusted hazard ratio for risk of 2-year cardiac mortality after DES versus BMS implantation was 0.49 (95% confidence interval 0.32 to 0.77). The benefit of DESs in reducing cardiac mortality was obtained in the period from 3 to 6 months and maintained up to 2 years. In conclusion, for patients with ULMCA stenosis undergoing PCI, DES implantation was associated with higher adjusted rates of 2-year survival free from cardiac death. The benefit of DESs in reducing cardiac mortality was obtained in the period in which clinical manifestations of restenosis usually peak.

A Prospective Randomized Trial of Thrombectomy Versus No Thrombectomy in Patients With ST-Segment Elevation Myocardial Infarction and Thrombus-Rich Lesions: MUSTELA (MUltidevice Thrombectomy in Acute ST-Segment ELevation Acute Myocardial Infarction) Trial

OBJECTIVES The aim of this study was to evaluate whether thrombectomy during primary percutaneous coronary intervention (pPCI) in patients with high thrombus burden improves myocardial reperfusion and reduces infarct size. BACKGROUND Thrombectomy aims at reducing distal thrombotic embolization during pPCI, improving myocardial reperfusion and clinical outcome. METHODS We randomized 208 patients with high thrombus burden in a 1:1 ratio to either pPCI with thrombectomy (Group T) or standard pPCI (Group S). Thrombectomy was performed with either rheolytic or manual aspiration catheters. Three-month magnetic resonance imaging was performed to assess infarct size and transmurality and microvascular obstruction (MVO). The primary endpoints were ST-segment elevation resolution (STR) >70% at 60 min and 3-month infarct size. RESULTS The baseline profile was similar between groups, except for a higher rate of initial Thrombolysis In Myocardial Infarction flow grade 3 in Group S (p = 0.002). Group T showed a significantly higher rate of STR (57.4% vs. 37.3%; p = 0.004) and of final myocardial blush 3 (68.3% vs. 52.9%; p = 0.03). Group T and Group S did not differ with regard to infarct size (20.4 ± 10.5% vs. 19.3 ± 10.6%; p = 0.54) and transmurality (11.9 ± 12.0% vs. 11.6 ± 12.7%; p = 0.92), but Group T showed significantly less MVO (11.4% vs. 26.7%; p = 0.02) and a higher prevalence of inhomogeneous scar (p < 0.0001). One-year freedom from major adverse cardiac events was similar between groups. CONCLUSIONS Thrombectomy as an adjunct to pPCI in patients with high thrombus load yielded better post-procedural STR and reduced MVO at 3 months but was not associated with a reduction in infarct size and transmurality. Thromboaspiration in Patients With High Thrombotic Burden Undergoing Primary Percutaneous (Coronary Intervention; NCT01472718).

Are drug-eluting stents superior to bare-metal stents in patients with unprotected non- bifurcational left main disease? Insights from a multicentre registry

AIMS To compare long-term clinical outcome following drug-eluting stents (DES) or bare-metal stents (BMS) implantation on lesions located at the ostium or the shaft of the left main in a large real-world population. The advent of DES decreased the risk of unprotected left main coronary artery (ULMCA) restenosis when compared with BMS, but it is unclear if this advantage continues when non-bifurcational lesions are considered. METHODS AND RESULTS The GISE-SICI registry is a retrospective, observational multicentre registry promoted by the Italian Society of Invasive Cardiology in which 19 high-volume participating centres enrolled 1453 consecutive patients who underwent percutaneous coronary intervention on ULMCA between January 2002 and December 2006. From the registry, a total of 479 consecutive patients with ostial and shaft lesions who underwent DES (n = 334) or BMS (n = 145) implantation were analysed with extensive multivariable and propensity score adjustments. At 3-year follow-up, risk-adjusted survival rates were higher in patients treated with DES than in those treated with BMS. The adjusted hazard ratio (HR) for the risk of mortality after DES implantation relative to BMS implantation was 0.37 (95% CI: 0.15-0.96, P = 0.04). The adjusted HR for the risk of cardiac mortality was 0.31 (95% CI: 0.09-1.04, P = 0.06). The adjusted 3-year rates of target lesion revascularization (TLR) were not significantly lower in the DES group than in the BMS group (P = 0.60). CONCLUSION In a large population of patients with lesions located at the ostium or the shaft of the left main in a real-world setting, DES were associated with favourable clinical outcomes when compared with BMS, although there was no evidence of a significant reduction in TLR with DES vs. BMS.

Deoxyribonucleic Acid Damage in Human Lymphocytes After Percutaneous Transluminal Coronary Angioplasty

UNLABELLED OBJECTIVES; We investigated the presence of oxidative deoxyribonucleic acid (DNA) damage in the peripheral lymphocytes of patients undergoing percutaneous transluminal coronary angioplasty (PTCA) by using the micronucleus test and comet assay, which are sensitive biomarkers of DNA damage. BACKGROUND; Although it has recognized that ischemia-reperfusion can induce oxidative DNA damage, its occurrence in patients undergoing PTCA has not yet been demonstrated. METHODS Three groups of patients were enrolled: 30 patients with documented coronary heart disease who underwent elective PTCA (group I); 25 patients who underwent elective coronary angiography for diagnostic purpose (group II); and 27 healthy, age- and gender-matched subjects (group III). For each subject, the frequency of micronucleated binucleated (MNBN) cells, DNA single-strand breaks (SSBs), endonuclease III-sensitive sites, and sites sensitive to formamidopyrimidine glycosylase (FPG) were analyzed before and after diagnostic procedures. RESULTS The mean basal values of MNBN cells (p = 0.04), DNA-SSBs (p = 0.001), endonuclease III-sensitive sites (p = 0.002), and FPG sites (p < 0.0001) were significantly higher in groups I and II than in group III. A high significant increase of MNBN cell frequency was observed in group I after the PTCA procedure (11.0 +/- 1.3 vs. 19.8 +/- 1.6, p < 0.0001), whereas no significant difference was observed in group II (10.2 +/- 1.3 vs. 12.9 +/- 1.4, p = 0.18). A significant positive correlation was observed between the increase in the MNBN cell rate and total inflation time during PTCA (R = 0.549, p = 0.0017). The levels of DNA-SSBs (11.7 +/- 1.4 vs. 26.5 +/- 3.0, p = 0.0003) and FPG sites (13.8 +/- 1.8 vs. 22.5 +/- 2.4, p = 0.01) were also higher after PTCA. CONCLUSIONS Our results provide evidence for oxidative DNA damage after PTCA, likely related to ischemia-reperfusion injury.