Leor Perl

Meta-Analysis of the Usefulness of Mitraclip in Patients With Functional Mitral Regurgitation

Midterm outcomes for patients presenting with heart failure and functional mitral regurgitation (MR) treated with Mitraclip remain unclear. Pubmed, Medline, and Google Scholar were systematically searched for studies enrolling patients with severe-moderate MR who underwent Mitraclip implantation. All events after at least 6 months were the primary safety end point (including death, rehospitalization for heart failure, and reinterventions), whereas change in the ejection fraction, left ventricular volumes, arterial pulmonary pressure, and left atrial diameters were considered as secondary end points. Meta-regression analysis was performed to evaluate the effect of baseline clinical and echocardiographic parameters on efficacy outcomes: 875 patients were included in 9 studies; 1.48 clips (1.3 to 1.7) for patients were implanted, and after a median follow-up of 9 months (6 to 12), 409 patients (78% [75% to 83%]) were in class New York Heart Association I/II and 57 (11% [8% to 14%]) still had moderate-to-severe MR. Overall adverse events occurred in 137 (26% [20% to 31%]) of the patients and 78 (15% [1% to 17%]) of them died; 6-minute walk test improved by 100 m (83 to 111), whereas a significant reduction in left ventricular volumes and systolic pulmonary pressure was reported. At meta-regression analysis, an increase in left ventricle systolic volumes positively affected reduction of volumes after Mitraclip, whereas atrial fibrillation reduced the positive effect of the valve implantation on ejection fraction on end-diastolic and -systolic volumes. In conclusion, Mitraclip represents an efficacious strategy for patients with heart failure and severe MR. It offers a significant improvement in functional class and in cardiac remodeling, in patients with severely dilated hearts as well, although its efficacy remains limited in the presence of atrial fibrillation.

Response to Prasugrel and Levels of Circulating Reticulated Platelets in Patients With ST-Segment Elevation Myocardial Infarction

OBJECTIVES The aim of this study was to determine whether response to prasugrel is associated with the proportion of circulating reticulated platelets (RPs) in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND Despite better pharmacodynamic properties and clinical efficacy of prasugrel compared with clopidogrel, antiplatelet responses to prasugrel are not uniform. The mechanism of this variability in response is not clear. RPs, young hyperactive forms, are increased during situations of enhanced platelet turnover. METHODS Patients with STEMI treated with primary percutaneous intervention (PCI) and prasugrel were tested for platelet reactivity using purinergic receptor P₂Y, G-protein coupled, 12 (P₂Y₁₂) assay and multiple electrode aggregometry (MEA). RP levels were determined using flow cytometry with thiazole orange staining. Tests were performed at 2 to 4 days and 30 days post-PCI. Platelet function was compared by varying levels of RPs, analyzed as continuous (regression analysis) and categorical (tertiles) variables. RESULTS Sixty-two patients were included (mean age: 57.5 ± 8 years; 21.2% women; 27.7% diabetes). At the early time point, RP levels were strongly correlated with platelet reactivity when evaluated by the P₂Y₁₂ assay (Spearmans correlation coefficient: 0.55 for P₂Y₁₂ reaction units, -0.49 for percent inhibition) and MEA (Spearmans: 0.50). The upper tertile of RPs displayed higher platelet reactivity compared with the middle and lower tertiles, according to P₂Y₁₂ assay and MEA. Similar results with strong correlations between RP and platelet reactivity were noted at 30 days post-PCI. CONCLUSIONS The proportion of circulating RPs strongly correlates with response to prasugrel in patients with STEMI treated with PCI. High levels of RPs are associated with increased platelet reactivity despite prasugrel treatment.

Long-term outcome of patients with antiphospholipid syndrome who undergo percutaneous coronary intervention.

Objectives: Patients with antiphospholipid antibody syndrome (APS) have an increased risk of atherothrombotic complications. There are limited data regarding the outcome of patients with APS who undergo percutaneous coronary intervention (PCI). Accordingly, we aimed to assess the long-term outcomes of these patients. Methods: Nineteen APS patients who underwent PCI between the years 2003 and 2008 were compared to 380 patients who had undergone PCI during the same period (PCI group) and were matched by age (±5 years), gender, diabetes and hypertension. In addition, APS patients were compared to 1,458 patients with ST segment elevation myocardial infarction (MI) who were treated with PCI during the same period. Six-month to 4-year clinical outcomes were evaluated. Results: The indication for PCI in the APS group was acute coronary syndrome in 52.6% of patients. After 1 year of follow-up, patients with APS had higher rates of target vessel revascularization than the other two groups, which translated to higher rates of major adverse cardiac events. There were no differences in MI or mortality rates between the groups. Conclusions: Patients with APS who undergo PCI have worse long-term clinical outcomes, driven by higher rates of revascularization, than other patients undergoing PCI. Further study is warranted to examine the mechanisms underlying these findings.

Circulating Endothelial Progenitor Cells in Patients With Dysfunctional Versus Normally Functioning Congenitally Bicuspid Aortic Valves

Patients with bicuspid aortic valve (BAV) may gradually develop significant valve dysfunction, whereas others remain free of dysfunction. Factors that determine the prognosis of BAV remain unclear. Because endothelial progenitor cells (EPCs) have a role in the repair of endothelial surfaces after injury, we hypothesized that EPCs may also be involved in preventing BAV degeneration. Accordingly, we compared EPC level and function in patients with BAV with versus without valve dysfunction. The study group included 22 patients with BAV and significant valve dysfunction (at least moderate aortic regurgitation and/or at least moderate aortic stenosis). The control group included 28 patients with BAV without valve dysfunction. All patients had 1 blood sample taken. Proportion of peripheral mononuclear cells expressing vascular endothelial growth factor receptor 2, CD133 and CD34 was evaluated by flow cytometry. EPC colony-forming units (CFUs) were grown from peripheral mononuclear cells, characterized, and counted after 7 days of culture. The 2 groups had similar clinical characteristics except for higher prevalence of hypertension in the dysfunctional valve group. Number of EPC CFUs was smaller in the dysfunctional valve group (32 CFUs/plate, 15 to 42.5, vs 48 CFUs/plate, 30 to 62.5, respectively, p = 0.01), and the migratory capacity of the cells in this group was decreased. In addition, the proportion of cells coexpressing vascular endothelial growth factor receptor 2, CD133, and CD34 tended to be smaller in the dysfunctional valve group. In conclusion, patients with BAV and significant valve dysfunction appear to have circulating EPCs with impaired functional properties. These findings require validation by further studies.

The EUROpean and Chinese cardiac and renal Remote Ischemic Preconditioning Study (EURO-CRIPS CardioGroup I): A randomized controlled trial

BACKGROUND The potential protective effects of remote ischemic preconditioning (RIPC) on contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) remain to be defined. METHODS AND RESULTS A double blind, randomized, placebo controlled multicenter study was performed. Patients younger than 85years old, with a renal clearance of 30-60ml/min/1.73m2, who were candidates for PCI for all clinical indications except for primary PCI, were allocated 1:1 to RIPC or to standard therapy. The primary endpoint was incidence of CIN. The secondary endpoint was incidence of peri-procedural myocardial infarction (PMI). From February 2013 to April 2014, 3108 patients who were scheduled for coronary angiography were screened for the study. 442 fulfilled the inclusion criteria and 223 received PCI. These patients were randomized to sham RIPC (n=107) or treatment group (n=116). The only pre-specified subgroup of diabetic patients included 85 (38%) cases. RIPC significantly reduced CIN incidence in the overall population (12.1% vs. 26.1%, p=0.01, with a NNT=9) and in non-diabetic patients (9.2% vs. 25.0%, p=0.02), but showed no benefit in diabetics (16.7% vs. 28.2%, p=0.21). A trend for lower PMI was seen in the intervention arm (creatine kinase - muscle brain >5 URL; 8.4% vs. 16.4%, p=0.07; troponin T >5 URL; 27% vs. 38%, p=0.21). CONCLUSIONS Remote ischemic preconditioning significantly reduces the incidence of acute kidney injury in non-diabetic patients undergoing PCI. Larger sample size is presumably needed to assess the effect of RIPC for patients with diabetes mellitus. Clinical Trial number:NCT02195726https://www.clinicaltrial.gov/.

Impact of female sex on long-term acute coronary syndrome outcomes.

ObjectivesRecent literature shows a greater risk for adverse clinical outcomes following acute coronary syndrome (ACS) events in women undergoing a percutaneous coronary intervention (PCI), especially in young and diabetic patients. We aimed to assess the impact of sex on clinical results following ACS. MethodsFrom our database of all-comer PCI patients, between 1 April 2004 and 31 December 2011, the procedural and angiographic results and clinical outcomes up to 5 years of 5819 patients with ACS undergoing emergent PCI were analyzed and compared according to sex. ResultsA total of 1425 (24.5%) of the patients were women. They presented at an older age (72.7±11.3 vs. 65.2±12.3 years, P<0.001), and more had diabetes mellitus (46.7 vs. 40.0%, P<0.001) and previous heart failure (12.1 vs. 7.26%, P=0.001). Mortality (21.63 vs. 13.22% at 5 years, P<0.001) and combined endpoints of death, myocardial infarction, and target-vessel revascularization (30.72 vs. 24.65% at 5 years, P<0.001) were higher in women. In a multivariate analysis using age, previous diabetes, heart failure, coronary artery bypass graft surgery, baseline glomerular filtration rate, presentation with ST-elevation myocardial infarction, and proximal left anterior descending artery disease, female sex was no longer an independent predictor of outcomes. No sex differences in mortality or major adverse cardiac events were observed in young or diabetic patients. ConclusionOur results show no sex differences in clinical endpoints among ACS patients undergoing PCI after correction for advanced age and comorbidities. Importantly, no differences were found in patients with diabetes mellitus or those younger than 60 years of age. This may reflect the importance of the administration of evidence-based therapeutics in women.

Prognosis of STEMI Patients with Multi-Vessel Disease Undergoing Culprit-Only PCI without Significant Residual Ischemia on Non-Invasive Stress Testing

Aims In about 50–80% of ST-segment elevation myocardial infarction (STEMI) patients there is significant atherosclerotic disease in other coronary arteries in addition to the culprit vessel. There is substantial controversy as to the optimal revascularization approach in these patients. We sought to compare the outcomes of STEMI patients with multi-vessel disease (MVD) treated with culprit-only primary percutaneous coronary intervention (PPCI) without significant ischemia on subsequent non-invasive testing, to those of STEMI patients with single-vessel disease (SVD). Methods and Results Between 2001–2010, 1,540 consecutive patients treated with primary PCI for STEMI were prospectively observed and entered into a comprehensive clinical database. The primary end point was a composite of major adverse cardiac events (MACE), consisting of mortality, re-infarction and revascularization within 1 and 3 years following PPCI (excluding events occurring during the first 30 days). Patients with cardiogenic shock were excluded. The study included 720 patients with SVD and 185 patients with MVD who underwent culprit-only PPCI and had no residual ischemia on subsequent non-invasive stress testing. Patients with MVD were older, more likely to have hypertension or previous MI and less likely to be smokers and present with anterior MI than patients with SVD. One and 3-year MACE rates were similar between the groups. On cox proportional-hazards regression MVD without residual ischemia was not independently associated with MACE and its components. Conclusions STEMI patients with MVD treated with culprit only-PCI without significant residual ischemia on non-invasive stress testing appear to have similar prognosis to STEMI patients with SVD.

Effects of prasugrel pretreatment on angiographic myocardial perfusion parameters in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

ObjectivePrasugrel is a third-generation thienopyridine, with significant pharmacodynamic and clinical advantages over clopidogrel. There are few data on the effects of prasugrel therapy, as compared with clopidogrel, in terms of perfusion during percutaneous coronary intervention (PCI), in patients with ST-elevation myocardial infarction (STEMI). MethodsA total of 128 patients with STEMI, pretreated with prasugrel 60 mg loading dose (mean age=55.9±9.1; 10.9% were women and 18.0% had diabetes), were compared with 128 propensity-matched patients pretreated with clopidogrel 600 mg (mean age=58.7±10.7; 10.2% were women and 19.5% had diabetes) for the primary endpoint of thrombolysis in myocardial infarction (TIMI) flow and myocardial blush grade at completion of the PCI. Secondary endpoints included the combined sum of major adverse events: death, reinfarction or target vessel revascularization at 1 year. ResultsMean TIMI flow grade pre-PCI was similar between the two groups (1.31±1.3 in the prasugrel group and 1.30±1.2 in the clopidogrel group, P=0.96). However, after intervention, it was higher in the prasugrel group (2.94±0.24 vs. 2.84±0.37, respectively, P=0.016), as was myocardial blush (2.70±0.76 vs. 2.31±0.52, respectively, P<0.001). The percentage of TIMI 3 after intervention was also higher in the prasugrel group (97.70 vs. 90.60%, P=0.02). The combined rate of major adverse events at 1 year (8.7 vs. 11.6%, P=0.11), as well as total mortality (3.1±5.6 vs. 4.7±9.1%, P=0.52), did not differ between the two groups. ConclusionIn patients with STEMI undergoing primary PCI, pretreatment with prasugrel resulted in better angiographic perfusion results, as compared with pretreatment with clopidogrel.

Monitoring platelet reactivity during prasugrel or ticagrelor washout before urgent coronary artery bypass grafting

Objectives Patients with acute myocardial infarction pretreated with prasugrel or ticagrelor may require urgent coronary artery bypass grafting (CABG). However, prasugrel and ticagrelor withdrawal period is recommended for 5–7 days before planned CABG to enable full platelet recovery. We hypothesized that monitoring sequential platelet reactivity (PR) could identify patients with early platelet recovery who may benefit from earlier surgery before the guideline-recommended 5–7 day delay. Patients and methods We performed preoperative PR assays in 35 patients with acute myocardial infarction who received prasugrel (60%) or ticagrelor (40%) and required an urgent CABG. When platelet inhibition levels were favorable, on the basis of the VerifyNow assay, surgery was endorsed. CABG-related bleeding parameters were collected and compared with two matched control groups composed of patients who received fewer potent antiplatelet regimens. Results On the basis of platelet function monitoring, we identified 21 (56.7%) patients with a relatively earlier platelet recovery who underwent CABG before the end of the conventional washout period (5–7 days). For these patients, the washout periods were shortened to an average time of 2.6±1.0 days for ticagrelor and 3.8±1.5 days for prasugrel. CABG-related bleeding parameters were comparable with the two matched control groups. Conclusion A strategy of performing preoperative PR assays can identify patients who recover platelet function in less than 5–7 days after ticagrelor or prasugrel discontinuation. This strategy may provide the basis for performing urgent CABGs earlier than the currently recommended delay. Future, larger studies are required to establish these preliminary findings.

Percutaneous coronary intervention of the left main artery before MitraClip implantation.

Functional mitral regurgitation (MR) is common in patients with ischemic cardiomyopathy. We present a case of an 83-year-old patient with ischemic heart disease and ischemic cardiomyopathy, who was repeatedly admitted for pulmonary edema and underwent a percutaneous trans-septal MitraClip procedure. During coronary angiography, a severe left main stenosis was demonstrated. Treatment included both percutaneous coronary intervention and the implantation of two MitraClip devices, with very good results. We believe that this case illustrates the need for comprehensive assessment of ischemia in patients with functional MR.