Impact of dual antiplatelet therapy duration on clinical outcome after coronary bifurcation stenting: results from the EuroBifurcation Club registry.

BACKGROUND: Optimal duration of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) of a bifurcation stenosis is still debated. We evaluated the impact of DAPT duration on clinical outcomes in all-comers patients undergoing bifurcation PCI included in the European Bifurcation Club (EBC) registry. METHODS: We enrolled 2284 consecutive patients who completed at least 18 months follow-up. The cumulative occurrence of major adverse cardiac and cardiovascular events (MACCE), defined as a composite of overall-death, non-fatal myocardial infarction (MI), target vessel revascularization (TVR) and stroke were evaluated. Bleedings classified as Bleeding Academic Research Consortium (BARC) ≥3 were evaluated too. RESULTS: Patients were divided into 3 groups: short DAPT (<6-months, N.=375); standard DAPT (≥6-months but ≤12-months, N.=636); prolonged DAPT (>12-months, N.=1273). At 24 months follow-up MACCE-free survival was significantly lower in short DAPT patients (Log-Rank: 45.23, P for trend <0.001). MACCE occurred less frequently in the prolonged DAPT group (148 [11.6%]) as compared with both the short (83 [22.1%] HR: 0.48 [0.37-0.63], P<0.001) and standard DAPT groups (137 [21.5%] HR:0.51 [0.41-0.65], P<0.001). These differences remain after propensity score adjustment (respectively, HR: 0.27 [0.20-0.36] and HR: 0.44 [0.34-0.57]). Such finding was consistent in patients presenting with both acute and chronic coronary syndromes. BARC≥3 bleedings were 0.3% in the standard DAPT, 1.6% in short and 1.9% in prolonged DAPT groups. CONCLUSIONS: In the "real-world" EBC registry of patients undergoing PCI of coronary artery bifurcation stenosis, a prolonged DAPT duration was associated with a significantly lower risk of MACCE and a potential increased risk of major bleedings.

Coronary angiography- or fractional flow reserve-guided complete revascularization in multivessel disease STEMI: A Bayesian hierarchical network meta-analysis.

AIMS: To identify the best strategy to achieve complete revascularization (CR) in patients with ST-elevation myocardial infarction (STEMI) and multi-vessel disease (MVD). METHODS AND RESULTS: We systematically reviewed the literature for randomized controlled trials (RCTs) comparing IRA-only PCI and CR guided by angiography or fractional flow reserve (FFR) in MVD-STEMI. Both frequentist (classical) and Bayesian network meta-analysis were performed, including a comparative hierarchy estimation of the probability to reduce the primary composite endpoint of all-cause death and new myocardial infarction (MI). We identified 11 RCTs, including 8193 STEMI patients. Compared with IRA-only strategy, CR significantly reduced the primary endpoint (OR: 0.73; 95%CI0.55-0.97). We observed non-significant difference between angiography and FFR guidance in reducing the primary endpoint (OR: 0.73, 95% CI 0.35-1.57). The Bayesian probability analysis ranked angio-guided CR as the best intervention yielding lowest risk of all-cause death or new MI (SUCRA92%). CONCLUSIONS: In patients with MVD-STEMI, CR is associated with a reduction in all-cause mortality and new MI compared with IRA-only PCI. Angio-guided CR is associated with the lowest risk of all-cause death or new MI, therefore the role of FFR-guidance in this setting is questionable. CONDENSED ABSTRACT: Both frequentist and Bayesian network meta-analysis were performed to compare infarct-related artery (IRA)-only percutaneous coronary intervention (PCI) and complete revascularization (CR) guided by angiography or fractional flow reserve (FFR) in multivessel disease (MVD) and acute ST-elevation myocardial infarction (STEMI). Eleven randomized controlled trials were identified, including 8193 STEMI patients. Compared with IRA-only strategy, CR significantly reduced the incidence of the composite endpoint of all-cause death and new myocardial infarction without significant difference in angio-guided and FFR-guided CR. The Bayesian probability analysis ranked angio-guided CR as the best intervention yielding lowest risk of the composite endpoint and, therefore the role of FFR-guidance in this setting is questionable.

The impact of the extent of side branch disease on outcomes following bifurcation stenting.

OBJECTIVES: To define the impact of side branch (SB) lesion length on clinical outcomes after percutaneous coronary intervention (PCI) on bifurcation lesions. BACKGROUND: The role of the SB lesion length remains questionable in PCI planning and its implication on clinical outcome is controversial. METHODS: Data from the retrospective multicenter EBC-P2BiTO registry were analyzed. The primary endpoint was the occurrence of major adverse cardiac events (MACE), defined as the composite of cardiac death, myocardial infarction excluding periprocedural, or stent thrombosis at 13 months median follow-up (IQR 11-28). By using propensity scores for inverse probability of treatment weighting (IPTW), the comparison of treatment groups was adjusted to correct for potential confounding. RESULTS: Among 1,252 patients, SB was normal in 489 (39%), diseased in 763 (61%) cases. MACE occurred in 68 patients (5.4%). The optimal discriminant SB lesion length for MACE was ≥10 mm, with an area under the curve of 0.71 (p < .01). The incidence of MACE was higher among patients with SB lesions ≥10 mm (8%) than with normal SB (4.1%) (hazard ratio [HR], 2.8; 95% confidence interval [CI], 1.5-5.3; p = .001, IPTW-adjusted) or SB lesions <10 mm (5.1%) (HR, 1.5; 95% CI, 1.1-3.3; p = .048, IPTW-adjusted), being similar between these last two groups. CONCLUSIONS: In bifurcation PCI, SB lesion length ≥ 10 mm identifies patients at higher risk of MACE than those with <10 mm SB lesions and those without SB disease, considering that no differences were observed among these last two groups. Careful planning is mandatory when approaching bifurcations with long SB lesions.

Calcific lesion preparation for coronary bifurcation stenting.

Bifurcating coronary lesions are a very common challenge in interventional cardiology because of the technical complexity in their treatment, the risk of side branch occlusion and an overall worse outcome when compared to non-bifurcating lesions. The presence of calcifications represents further complexity due to the difficulty in device delivery and stent expansion as well as enhanced risk of side branch occlusion. Rotational and orbital atherectomy, scoring and cutting balloons, coronary lithoplasty are available tools which have been introduced over the last three decades to overcome such issue. Nevertheless, their application in different contexts of bifurcations presents specific caveats and the studies directed at comparing such techniques have never been expressly oriented in the subset of the bifurcating lesion. In this paper, we review these devices and their usefulness in bifurcations by analyzing consistent data from clinical trials, and we propose a practical algorithm for the treatment of severely calcified bifurcating lesions according to their anatomical features.

Cardiac MR With Late Gadolinium Enhancement in Acute Myocarditis With Preserved Systolic Function: ITAMY Study.

BACKGROUND: The prognostic role of cardiac magnetic resonance (CMR) and late gadolinium enhancement (LGE) has not been clarified in acute myocarditis (AM) with preserved left ventricular (LV) ejection fraction (EF). OBJECTIVES: This study sought to evaluate the role of CMR and LGE in the prognosis of AM with preserved LVEF. METHODS: This study analyzed data from ITAMY (ITalian multicenter study on Acute MYocarditis) and evaluated CMR results from 386 patients (299 male; mean age 35 ± 15 years) with AM and preserved LVEF. Clinical follow-up was performed for a median of 1,572 days. A clinical combined endpoint of cardiac death, appropriate implantable cardioverter-defibrillator firing, resuscitated cardiac arrest, and hospitalization for heart failure was used. RESULTS: Among the 374 patients with suitable images, LGE involved the subepicardial layer inferior and lateral wall in 154 patients (41%; IL group), the midwall layer of the anteroseptal wall in 135 patients (36%; AS [anteroseptal] group), and other segments in 59 patients (16%; other-LGE group), and it was absent in 26 patients (no-LGE group). The AS group had a greater extent of LGE and a higher LV end-diastolic volume index than other groups, but levels of inflammatory markers were lower than in the other groups. Kaplan-Meier curve analysis indicated that the AS group had a worse prognosis than the other groups (p < 0.0001). Finally, in multivariable analysis, AS LGE was the best independent CMR predictor of the combined endpoint (odds ratio: 2.73; 95% confidence interval: 1.2 to 5.9; p = 0.01). CONCLUSIONS: In patients with AM and preserved LVEF, LGE in the midwall layer of the AS myocardial segment is associated with a worse prognosis than other patterns of presentation.

The acute impact of high-dose lipid-lowering treatment on endothelial progenitor cells in patients with coronary artery disease-The REMEDY-EPC early substudy.

RATIONALE AND OBJECTIVE: Endothelial progenitor cells (EPCs) play a role in vascular repair, while circulating endothelial cells (CECs) are biomarkers of vascular damage and regeneration. Statins may promote EPC/CEC mobilization in the peripheral blood. We evaluated whether pre-procedural exposure to different lipid-lowering drugs (statins±ezetimibe) can acutely increase levels/activity of EPCs/CECs in patients with stable coronary artery disease (CAD). METHODS: In a planned sub-analysis of the Rosuvastatin For REduction Of Myocardial DamagE During Coronary AngioplastY (REMEDY) trial, 38 patients with stable CAD on chronic low-dose statin therapy were randomized, in a double-blind, placebo-controlled design, into 4 groups before PCI: i. placebo (n = 11); ii. atorvastatin (80 mg+40 mg, n = 9); iii. rosuvastatin (40 mg twice, n = 9); and iv. rosuvastatin (5 mg) and ezetimibe (10 mg) twice, (n = 9). At baseline and 24 h after treatment-before PCI-, patients underwent blinded analyses of EPCs [colony forming units-endothelial cells (CFU-ECs), endothelial colony-forming cells (ECFCs) and tubulization activity] and CECs in peripheral blood. RESULTS: We found no significant treatment effects on parameters investigated such as number of CECs [Median (IQR): i. 0(0), ii. 4.5(27), iii. 1.9(2.3), iv. 1.9(2.3)], CFU-ECs [Median (IQR): i. 27(11), ii. 19(31), iii. 47(36), iv. 30(98)], and ECFCs [Median (IQR): i. 86(84), ii. 7(84), iii. 8/(42.5), iv. 5(2)], as well as tubulization activity [total tubuli (well), Median (IQR): i. 19(7), ii. 5(4), iii. 25(13), iv. 15(24)]. CONCLUSIONS: In this study, we found no evidence of acute changes in levels or activity of EPCs and CECs after high-dose lipid-lowering therapy in stable CAD patients.

ST segment/heart rate hysteresis improves the diagnostic accuracy of ECG stress test for coronary artery disease in patients with left ventricular hypertrophy.

BACKGROUND: The exercise electrocardiographic stress test (ExET) is the most widely used non-invasive diagnostic method to detect coronary artery disease. However, the sole ST depression criteria (ST-max) have poor specificity for coronary artery disease in patients with left ventricular hypertrophy. We hypothesised that ST-segment depression/heart rate hysteresis, depicting the relative behaviour of ST segment depression during the exercise and recovery phase of the test might increase the diagnostic accuracy of ExET for coronary artery disease detection in such patients. METHODS: In three cardiology centres, we studied 113 consecutive patients (mean age 66 ± 2 years; 88% men) with hypertension-related left ventricular hypertrophy at echocardiography, referred to coronary angiography after an ExET. The following ExET criteria were analysed: ST-max, chronotropic index, heart rate recovery, Duke treadmill score, ST-segment depression/heart rate hysteresis. RESULTS: We detected significant coronary artery disease at coronary angiography in 61 patients (53%). At receiver-operating characteristic analysis, ST-segment depression/heart rate hysteresis had the highest area under the curve value (0.75, P < 0.001 when compared with the 'neutral' receiver-operating characteristic curve value of 0.5). Area under the curve values were 0.68 (P < 0.01) for the chronotropic index, 0.58 (P = NS) for heart rate recovery, 0.57 (P = NS) for ST-max and 0.52 (P = NS) for the Duke treadmill score. CONCLUSIONS: Among currently available ExET diagnostic variables, ST-segment depression/heart rate hysteresis offers a substantially better diagnostic accuracy for coronary artery disease than conventional criteria in patients with hypertension-related left ventricular hypertrophy.

A fast and effective method to assess myocardial hyperemia in acute myocarditis by magnetic resonance.

Current cardiac magnetic resonance (CMR) quantitative signs for the diagnosis of myocarditis include myocardial edema, fibrosis and myocardial hyperemia (Hyp). Methods for the assessment of Hyp are actually complex and time-consuming. To test a simple and fast method to assess Hyp, using contrast enhancement steady state free precession (ceSSFP) technique. CMR imaging at 1.5T was performed on 39 patients with diagnosis of acute myocarditis and in 20 healthy controls. Hyp was evaluated in systolic and diastolic frames (Hyp-SYS and Hyp-DIA) as areas of myocardial hyperintensity in ceSSFP images early after gadolinium injection. Myocardial edema was evaluated using T2-STIR images. Myocardial fibrosis was assessed in conventional late gadolinium enhancement (LGE) images. A value of ≤12.1 g of Hyp-DIA was obtained as cut-off of normality in healthy controls. Using this threshold, Hyp was detected in 30 patients (77 %) with myocarditis. LGE was detected in 36 patients (92 %), and myocardial edema in 38 (97 %) patients with myocarditis A linear relation was found between Hyp-DIA and the extent of myocardial edema (R(2) 0.48, 95 % CI 0.47-0.85, p < 0.001) and the extent of LGE (R(2) 0.41, 95 % CI 0.31-0.61, p < 0.001). Patients with hyperemia had higher levels of C-reactive protein (p < 0.001), a higher extent of LGE (p < 0.05) and a larger left atrial area (p < 0.05). ceSSFP sequence at CMR is a novel and fast method to assess myocardial hyperemia in patient with acute myocarditis. Compared with non-Hyp subjects, patients with Hyp had more signs of inflammation and myocardial damage.

Safety and efficacy of G-CSF in patients with ischemic heart failure: the CORNER (Cell Option For Recovery in the Non-Eligible Patients for Revascularization) study.

BACKGROUND: Demonstration that the heart is not a post-mitotic organ has led to clinical trials trying to obtain myocardial repair even in patients with heart failure. AIM OF THE STUDY: To evaluate as a less invasive method for promoting cardiac repair. METHODS: Thirteen patients with ischemic heart failure in NYHA and/or CCS classes ≥ 3 unsuitable for revascularization received G-CSF, as a compassionate use, in addition to optimal medical therapy. Symptoms and cardiac perfusion by gated-SPECT were assessed at baseline and at 4 month follow up. RESULTS: G-CSF was generally well tolerated. NYHA and CCS classes improved significantly from 3 (IR 2.5-3) to 2 (IR 1-2.5) (p = 0.012) and from 3 (IR 1-3) to 1 (IR 1-2) (p = 0.033). Heart failure severity symptoms according to the Minnesota Living with Heart Failure Questionnaire scores exhibited a non significant improvement from 52 ± 27 to 39 ± 26 (p = 0.15). At the Seattle Angina Questionnaire scores (ranging from 0 to 100, higher scores indicating better status), physical limitation improved from 39 ± 31 to 64 ± 29 (p = 0.03), angina stability from 42 ± 29 to 64 ± 28 (p = 0.05), angina frequency from 53 ± 33 to 73 ± 26 (p = 0.04), treatment satisfaction from 67 ± 29 to 83 ± 21 (p = 0.07), disease perception from 37 ± 29 to 66 ± 26 (p = 0.007). Quality of life assessed by a Visual Analogue Scale improved from 33 ± 24 to 64 ± 20 mm (p = 0.003). Stress and differential regional perfusion scores improved significantly from 1.78 ± 1.38 to 1.66 ± 1.38 (p = 0.05) and from 0.35 ± 0.68 to 0.23 ± 0.53 (p = 0.02) respectively. CONCLUSIONS: In patients with ischemic heart failure unsuitable for revascularization, G-CSF is associated to a significant improvement of symptoms, possibly reducing stress-induced ischemia.

From bone marrow to the arterial wall: the ongoing tale of endothelial progenitor cells.

Several physiological and pathophysiological stimuli or drugs modulate endothelial progenitor cell (EPC) mobilization. Moreover, levels of circulating EPCs predict cardiovascular risk and left ventricular remodelling after myocardial infarction. Nevertheless, our understanding in this field is complicated by lack of an unequivocal definition of EPCs, thus limiting their clinical applications. This review summarizes current knowledge and uncertainties on EPC characterization and mobilization in the attempt to define their role in the management of cardiovascular diseases.