Enrico Favaretto

Postconditioning during coronary angioplasty in acute myocardial infarction: the POST-AMI trial

BACKGROUND Postconditioning (PC) has been suggested to reduce myocardial damage during primary percutaneous coronary intervention (PPCI), nevertheless clinical experience is limited. We aimed to explore the cardioprotective effect of PC using cardiac magnetic resonance (CMR) in ST-elevation myocardial infarction (STEMI) patients treated by PPCI. METHODS A total of 78 patients with first STEMI (aged 59±12 years) referred for PPCI, were stratified for STEMI location and randomly assigned to conventional PPCI or PPCI with PC. All patients, with occluded infarct related artery and no collateral circulation, received abciximab intravenously before PPCI. After reperfusion by effective direct stenting, control subjects underwent no further intervention, while in treated patients PC was performed within 1 min of reflow by 4 cycles of 1-minute inflation and 1-minute deflation of the angioplasty balloon. Primary end-point was infarct size (IS) reduction, expressed as percentage of left ventricle mass assessed by delayed enhancement on CMR at 30±10 days after index PPCI. RESULTS All baseline characteristics but diabetes (p=0.06) were balanced between groups. Postconditioning patients trended toward a larger IS compared to those treated by standard PPCI (20±12% vs 14±10%, p=0.054). After exclusion of diabetics, PC group still showed a trend to larger IS (p=0.116). Major adverse events seem to be more frequent in PC group irrespective to diabetic status (p=0.053 and p=0.080, respectively). CONCLUSIONS This prospective, randomized trial suggests that PC did not have the expected cardioprotective effect and on the contrary it might harm STEMI patients treated by PPCI plus abciximab. (Clinical Trial Registration-unique identifier: NCT01004289).

LAD Coronary Artery Myocardial Bridging and Apical Ballooning Syndrome

OBJECTIVES This study sought to evaluate the prevalence and potential role of myocardial bridging in the pathogenesis of apical ballooning syndrome (ABS). BACKGROUND ABS is characterized by reversible left ventricular dysfunction, frequently precipitated by a stressful event, but the pathogenesis remains still unclear. METHODS Forty-two consecutive patients (40 female, mean age 66 ± 7 years) with ABS underwent echocardiography, cardiac magnetic resonance, coronary angiography (CA) with intravascular ultrasound, and computed tomography angiography (CTA). Myocardial bridging was diagnosed by CA when a dynamic compression phenomenon was observed in the coronary artery and by CTA when a segment of coronary artery was completely (full encasement) or incompletely (partial encasement) surrounded by the myocardium. The prevalence of myocardial bridging detected by CTA and CA in ABS patients was compared with 401 controls without ABS who underwent both CTA and CA. RESULTS Myocardial bridging by CTA was observed in 32 ABS patients (76%): 23 with partial encasement and 9 with full encasement. All myocardial bridging was located in the mid segment of the left anterior descending coronary artery (LAD) with a mean length of 17 ± 9 mm. CA revealed myocardial bridging in 17 subjects (40%) (9 with partial encasement and 8 with full encasement by CTA). All subjects in which dynamic compression was observed by CA showed myocardial bridging by CTA, while none of the subjects with negative findings for myocardial bridging by CTA revealed dynamic compression by CA. Compared with controls, ABS patients showed a significant higher prevalence of myocardial bridging in the LAD either by CA (40% vs. 8%; p < 0.001) or by CTA (76% vs. 31%; p < 0.001). CONCLUSIONS Our study showed that myocardial bridging of the LAD is a frequent finding in ABS patients as revealed both by CA and, mostly, by CTA, suggesting a role of myocardial bridging as potential substrate in the pathogenesis of ABS.

PCI versus CABG for multivessel coronary disease in diabetics

Objectives: To explore the clinical performance of a strategy of revascularization by percutaneous coronary intervention (PCI) with drug‐eluting stent (DES) in diabetic patients with multivessel disease (MVD) compared with coronary artery bypass graft (CABG), when it is based on clinical judgment. Background: Diabetes mellitus (DM) is a major risk factor for poor outcome after PCI. However, PCI may result in better outcome if the choice of revascularization (PCI versus CABG) is based on the physician decision, rather than randomization. Limited experiences have compared revascularization by DES‐PCI versus CABG in DM patients with MVD. Methods: From August 2004 to August 2005, 220 consecutive DM patients with MVD underwent DES‐PCI (93) or CABG (127) at our Institution. The type of revascularization was dependent on patient and/or physician choice. Major adverse cardiac and cerebrovascular events (MACCE) included death, myocardial infarction, repeat coronary revascularization, and stroke. Results: Compared with PCI patients, CABG patients had higher prevalence of 3‐vessel disease (P < 0.001), significant LAD involvement (P < 0.001), presence of total occlusions (P = 0.04), collateral circulation (P < 0.001). At 2‐year follow‐up, MACCE were not different between CABG group and DES‐PCI group (OR 1.2; P = 0.6) and, only when the clinical judgment on the revascularization choice was excluded at propensity analysis, DES‐PCI increased the risk of 24‐month MACCE in total population (OR 1.8; P = 0.04). Conclusions: For patients with DM and MVD, a clinical judgment‐based revascularization by DES‐PCI is not associated with worse 2‐year outcome compared with CABG.

Valve Replacement for Severe Aortic Stenosis With Low Transvalvular Gradient and Left Ventricular Ejection Fraction Exceeding 0.50

BACKGROUND Severe aortic stenosis with a low transvalvular gradient and preserved left ventricular ejection fraction (LVEF) is often misdiagnosed, leading to undertreatment of such patients with no clear indication for surgical intervention. This study investigated the outcome of aortic valve replacement (AVR) in patients with severe aortic stenosis and a low transvalvular gradient despite normal LVEF. METHODS Between 1985 and 2008, we evaluated 73 patients who underwent AVR compared with 29 patients who did not. Overall, aortic valve area was 1.0 cm2 or smaller, LVEF was 0.50 or higher, and transvalvular gradient was 30 mm Hg or less. Multivariate and Cox analyses were used to compare these two groups according to AVR. RESULTS Compared with controls, AVR patients were younger and with higher body mass index. Coronary artery bypass grafting was performed simultaneously in 38 AVR patients (52%). At follow-up (median, 42 months; interquartile range, 23 to 75 months), survival was longer in AVR patients. By Cox analysis, AVR remained a major predictor of lower mortality (hazard ratio, 0.237; 95% confidence interval, 0.119 to 0.470; p<0.0001). CONCLUSIONS In patients with severe aortic stenosis and low transvalvular gradient despite a normal LVEF, AVR was associated with significant improvement in long-term survival and functional status and with a low operative mortality.

Transthoracic echocardiographic imaging of coronary arteries: tips, traps, and pitfalls.

The aim of this paper is to highlight coronary investigation by transthoracic Doppler evaluation. This application has recently been introduced into clinical practice and has received enthusiastic feedback in terms of coronary flow reserve evaluation on left anterior coronary artery disease diagnosis. Such diagnosis represents the most important clinical application but has in itself some limitations regarding anatomical and technological knowledge. The purpose of this paper is to offer a didactic approach on how to investigate the different segments of left anterior and posterior descending coronary arteries by transthoracic ultrasound using different anatomical key structures .as markersWe will conclude by underlining that, nowadays, innovative technology allows complete evaluation of both major coronary arteries in many patients in a resting condition as well as during pharmacology stress-tests, but we often do not know it.

Impact of multivessel coronary artery disease on early ischemic injury, late clinical outcome, and remodeling in patients with acute myocardial infarction treated by primary coronary angioplasty.

ObjectiveThe mechanism through which multivessel coronary artery disease (MVD) adversely affects the outcome of patients with ST-elevation myocardial infarction (STEMI) is poorly characterized. We assessed whether the impact of MVD on outcome of STEMI patients is because of ischemic damage after primary percutaneous coronary intervention (PPCI) or to late ischemic events. MethodsFrom August 2005 to 2007, 288 STEMI patients treated by (bare metal) stent-PPCI were prospectively enrolled. The ischemic injury early after PPCI (evaluated by multiparametric approach) and the incidence of late adverse cardiovascular events were compared between the two groups. ResultsCompared with single vessel coronary artery disease, MVD patients (n=134) were older, with higher prevalence of diabetes, prior MI, anterior MI and higher collateral score. Myocardial perfusion as assessed by myocardial blush and ΣST-segment resolution was similar in the two groups as well as the infarct size and microvascular obstruction as assessed by Troponin I and by the delayed enhancement of cardiac magnetic resonance. At clinical (98% complete) and echocardiogaphic (94% complete) follow-up (median 32 months) MVD patients showed a higher incidence of re-MI (6.1 vs. 1.3%), and urgent revascularization (8.3 vs. 2.7%) and worse left ventricular remodeling than single vessel disease patients. At propensity adjusted analysis MVD was an independent predictor of re-MI (odds ratio: 5.7) and ventricular remodeling (odds ratio: 2.2). ConclusionThe impact of MVD on clinical outcome and remodeling of STEMI patients is not because of the extent of ischemic damage observed after PPCI, but to recurrent ischemic events during follow-up.

Sirolimus- Versus Paclitaxel-Eluting Stents for the Treatment of Cardiac Allograft Vasculopathy

OBJECTIVES The aim of this study was to compare outcomes after percutaneous coronary intervention (PCI) with sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in the treatment of cardiac allograft vasculopathy (CAV). BACKGROUND PCI in patients with CAV is associated with increased rates of restenosis compared with PCI in patients without CAV. There are no dedicated studies on the influence of different drug-eluting stents (DES) on the outcomes of patients with CAV. METHODS This is a retrospective observational study of 108 consecutive patients with CAV who underwent PCI with SES and PES at UCLA Medical Center and University of Padova Medical Center between 2002 and 2008. RESULTS Baseline characteristics were similar among SES (n = 68) and PES (n = 40) patients with the exception of older patients, larger minimal lumen diameter, and smaller diameter stenosis in the SES-treated patients. Angiographic follow-up at 1 year was high in the SES and PES groups (74% vs. 76%, p = 0.8). The SES and PES groups had similar binary restenosis rates (10% vs. 9%, p = 0.7), percent diameter stenosis (24 +/- 24% vs. 24 +/- 18%, p = 0.94), and late lumen loss (0.67 +/- 1.03 mm vs. 0.68 +/- 1.11 mm, p > 0.9). One-year clinical outcomes were not significantly different among CAV patients treated with either SES or PES (major adverse cardiac events: 10% vs. 15%, p = 0.5; death: 3% vs. 5%, p = 0.4; myocardial infarction: 3% vs. 5%, p = 0.4; target vessel revascularization: 4% vs. 8%, p = 0.3). CONCLUSIONS In patients who underwent PCI for CAV, both SES and PES were safe and effective with no significant differences in clinical and angiographic outcomes. Randomized clinical trials comparing different DES with longer follow-up are necessary to identify the optimal treatment strategy for patients with CAV.

Design and Methodologies of the POSTconditioning during Coronary Angioplasty in Acute Myocardial Infarction (POST-AMI) Trial

Background: Reperfusion remains the definitive treatment for acute myocardial infarction (AMI), but restoring blood flow carries the potential to exacerbate the ischemia-related injury. Postconditioning might modify reperfusion-induced adverse events. Study Design: The POSTconditioning during Coronary Angioplasty in Acute Myocardial Infarction (POST-AMI) trial is a single-center, prospective, randomized study, with a planned inclusion of 78 patients with ST-elevation AMI. Patients will be randomly assigned to the postconditioning arm [primary angioplasty (PA) and stenting followed by brief episodes of ischemia-reperfusion early after recanalization] or non-postconditioning arm. All patients will be treated medically according to current international guidelines, including glycoprotein IIb/IIIa inhibitors before PA. The primary end point is to evaluate whether postconditioning, compared to plain PA, reduces infarct size estimated by cardiac magnetic resonance (CMR) at 30 ± 10 days after the AMI. Secondary end points are microvascular obstruction observed at CMR, ST-segment resolution, angiographic myocardial blush grade <2, non-sustained/sustained ventricular tachycardia in the 48 h following PA, left ventricular remodeling and function at follow-up CMR, and the reduction of major adverse cardiac events at 30 days and 6 months. Conclusion: The POST-AMI trial will evaluate the usefulness of postconditioning in limiting infarct size during the early and late phases after AMI.

Meta-analysis of randomized trials of postconditioning in ST-elevation myocardial infarction.

Clinical benefit of postconditioning in patients with ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention is still controversial. We performed a meta-analysis of available randomized clinical trials (RCTs) to define the role of postconditioning in STEMI. Fourteen RCTs evaluating postconditioning in a total of 778 patients with STEMI were identified in PubMed, EMBase, and Cochrane databases from January 1998 to February 2014. Overall, postconditioning was found to be cardioprotective in term of infarct size reduction (weighted standardized mean differences -0.5837, 95% confidence interval -0.9609 to -0.2066, p <0.05), but significant heterogeneity across the trials was detected (I(2) = 84%). Univariate meta-regression analysis did not identify clinical or procedural variables associated with a more pronounced effect of postconditioning effects on infarct size with the exception of using cardiac magnetic resonance (CMR) to evaluate infarct size (p <0.01). Restricting the analysis to 6 RCTs including a total of 448 patients and evaluating the postconditioning effect on infarct size by means of CMR led to the disappearance of benefit of postconditioning on infarct size. In conclusion, the results of this meta-analysis of RCTs suggested that postconditioning reduces infarct size, as expressed by weighted standardized mean differences. However, if the analysis was limited to trials with a more accurate quantification of infarct size reduction, namely by CMR, the benefit was lost. More data are required before adoption of postconditioning in clinical practice.

Comparison between sirolimus- and paclitaxel-eluting stents for the treatment of older patients affected by coronary artery disease: results from a single-center allcomers registry

The treatment of elderly patients with coronary artery disease (CAD) is challenging because this population is complex and greatly expanding. Drug-eluting stents (DES) generally improve the outcome in high-risk cases. We evaluated the clinical impact of different first-generation DES, i.e., sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES), in this context. A prospective, nonrandomized, single-center, allcomers registry consecutively enrolling all patients aged ≥75 years eligible for percutaneous coronary intervention (PCI) with DES was carried out. Only one type of DES was implanted per protocol for each patient. Two groups were identified according to the type of implanted stent, i.e., SES and PES. The primary end point encompassed major adverse cardiac events (MACE), including death, myocardial infarction, and target lesion revascularization (TLR). The secondary end point encompassed the rate of definite/probable stent thrombosis and target vessel revascularization (TVR). From June 2004 to May 2008, 151 patients were enrolled. Among them, 112 (74.2%) received SES and 39 (25.8%) received PES. Baseline clinical characteristics were similar, while few angiographic features (ostial location, stent diameter, proximal reference vessel diameter) showed minor differences. At the median follow-up of 22.6 months, primary and secondary end points did not significantly differ in terms of MACE (SES 12.5% vs PES 20.5%, P = 0.3), death (SES 5.4% vs PES 7.7%, P = 0.7), myocardial infarction (SES 4.5% vs PES 10.3%, P = 0.2), TLR (SES 2.7% vs PES 2.6%, P = 1.0), stent thrombosis (SES 1.8% vs PES 5.1%, P = 0.3), and TVR (SES 1.8% vs PES 0%, P = 0.6). In this real-world population of elderly patients treated by DES–PCI for CAD, the overall efficacy and safety have been excellent in both DES, and the choice between SES and PES did not influence the clinical outcome.