Long-term clinical outcome after intracoronary application of bone marrow-derived mononuclear cells for acute myocardial infarction: migratory capacity of administered cells determines event-free survival.

BACKGROUND: In the REPAIR-AMI trial, intracoronary infusion of bone marrow-derived cells (BMCs) was associated with a significantly greater recovery of contractile function in patients with acute myocardial infarction (AMI) at 4-month follow-up than placebo infusion. The current analysis investigates clinical outcome and predictors of event-free survival at 5 years. METHODS AND RESULTS: In the multicentre, placebo-controlled, double-blind REPAIR-AMI trial, 204 patients received intracoronary infusion of BMCs (n = 101) or placebo (n = 103) into the infarct vessel 3-7 days following successful percutaneous coronary intervention. Fifteen patients died in the placebo group compared with seven patients in the BMC group (P = 0.08). Nine placebo-treated patients and five BMC-treated patients required rehospitalization for chronic heart failure (P = 0.23). The combined endpoint cardiac/cardiovascular/unknown death or rehospitalisation for heart failure was more frequent in the placebo compared with the BMC group (18 vs. 10 events; P = 0.10). Univariate predictors of adverse outcomes were age, the CADILLAC risk score, aldosterone antagonist and diuretic treatment, changes in left ventricular ejection fraction, left ventricular end-systolic volume, and N-terminal pro-Brain Natriuretic Peptide (all P < 0.01) at 4 months in the entire cohort and in the placebo group. In contrast, in the BMC group, only the basal (P = 0.02) and the stromal cell-derived factor-1-induced (P = 0.05) migratory capacity of the administered BMC were associated with improved clinical outcome. CONCLUSION: In patients of the REPAIR-AMI trial, established clinical parameters are associated with adverse outcome at 5 years exclusively in the placebo group, whereas the migratory capacity of the administered BMC determines event-free survival in the BMC-treated patients. These data disclose a potency-effect relationship between cell therapy and long-term outcome in patients with AMI.

Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction.

BACKGROUND: Pilot trials suggest that the intracoronary administration of autologous progenitor cells may improve left ventricular function after acute myocardial infarction. METHODS: In a multicenter trial, we randomly assigned 204 patients with acute myocardial infarction to receive an intracoronary infusion of progenitor cells derived from bone marrow (BMC) or placebo medium into the infarct artery 3 to 7 days after successful reperfusion therapy. RESULTS: At 4 months, the absolute improvement in the global left ventricular ejection fraction (LVEF) was significantly greater in the BMC group than in the placebo group (mean [+/-SD] increase, 5.5+/-7.3% vs. 3.0+/-6.5%; P=0.01). Patients with a baseline LVEF at or below the median value of 48.9% derived the most benefit (absolute improvement in LVEF, 5.0%; 95% confidence interval, 2.0 to 8.1). At 1 year, intracoronary infusion of BMC was associated with a reduction in the prespecified combined clinical end point of death, recurrence of myocardial infarction, and any revascularization procedure (P=0.01). CONCLUSIONS: Intracoronary administration of BMC is associated with improved recovery of left ventricular contractile function in patients with acute myocardial infarction. Large-scale studies are warranted to examine the potential effects of progenitor-cell administration on morbidity and mortality.

Rotational atherectomy in CTO lesions: too risky? Outcome of rotational atherectomy in CTO lesions compared to non-CTO lesions.

AIMS: The aim of this study was to determine the feasibility of rotational atherectomy (RA) in chronic total occlusion (CTO) PCI and compare the success and complication rates of RA in CTO lesions versus non-occluded lesions. Data on RA in CTO are rare and it is unknown how procedural success and risk of RA in CTO lesions compare to RA in non-CTO lesions. METHODS AND RESULTS: RA was performed in 392 out of 17,919 PCI procedures (2.2% of the PCI cohort) and classified as RA CTO (n=75) and RA non-CTO (n=317). Procedural success and MACCE in both groups were assessed by two investigators. All RA procedures were analysed for dissections prior to RA, which were defined according to the NHLBI classification. Baseline characteristics were not significantly different in the two groups but, in RA CTO, lesion type was more complex (p<0.001), stented segments were longer (35.0±22.7 vs. 46.0±24.8 mm, p<0.001) and mean burr size was smaller (1.61±0.17 vs. 1.49±0.18 mm, p<0.001). Procedural success and complications were not different (RA non-CTO 96.2% and RA CTO 94.7%, RA non-CTO 2.5% and RA CTO 4.0%, respectively). RA performed in dissection planes had a 100% procedure success rate in CTO and a 92% success rate in non-CTO. CONCLUSIONS: RA in CTO is as safe and as effective as RA in non-CTO. The presence of dissections prior to RA in CTO lesions as well as in non-CTO lesions does not seem to have a negative impact on outcome.

Drug eluting balloons as stand alone procedure for coronary bifurcational lesions: results of the randomized multicenter PEPCAD-BIF trial.

OBJECTIVES: We set out to investigate the benefit of distal main or side branch treatment with a DCB compared to POBA in coronary bifurcation lesions. BACKGROUND: The standard treatment of bifurcation lesions is application of a DES to the main branch with provisional side branch stenting. While this resulted in considerable improvement in overall MACE rate suboptimal side branch results remained a problem. METHODS: The study was performed from 2011 to 2013 in six German centers. Native bifurcation lesions were included if side branch vessel diameter was ≥2 and ≤3.5 mm and no proximal main branch lesions was found. After successful predilatation randomization was performed to either DCB application or no further treatment. Follow-up angiograms for QCA analysis were done after 9 months. Primary endpoint was late lumen loss (LLL). RESULTS: 64 patients were successfully randomized. Minimal lumen diameter and grade of stenosis were equal in both groups. Only five stents were used as bail out. Angiographic follow-up was achieved in 75 % of patients. No patient died. There was one NSTEMI in the POBA group. Restenosis rate was 6 % in the DCB group vs 26 % in the POBA group (p = 0.045). TLR was necessary in one patient of the DCB group vs three patients of the POBA. The primary endpoint LLL was 0.13 mm in the DCB vs 0.51 mm in the POBA group (p = 0.013). CONCLUSION: In bifurcation lesions that show only class A or B dissection and recoil not beyond 30 % the use of DCBs is a sound strategy.

Focal ischemia of the brain after neuroprotected carotid artery stenting.

OBJECTIVES: This study sought to assess the incidence of cerebral ischemia in nonselected patients undergoing neuroprotected carotid angioplasty and stenting (CAS) without preceding multiple-vessel diagnostic angiography. BACKGROUND: Protection devices to prevent distal embolization during CAS are presently under clinical investigation. Diffusion-weighted magnetic resonance imaging (MRI) visualizes recent ischemia of the brain and may aid in assessing the efficacy of protection devices. METHODS: Elective CAS was performed in 42 consecutive patients (15 female, 27 male; mean age, 67 +/- 9 years) using six different types of cerebral protection systems. All patients underwent MRI of the brain before and after a total of 44 interventions. RESULTS: Placement and retrieval of the devices and stent deployment was achieved in all procedures. New ischemic foci were seen on postinterventional MRI in 10 cases (22.7%). One patient had sustained a major stroke, whereas no adverse neurological sequelae were associated with the other nine procedures. In the latter, one to three foci (maximum area 43.0 mm(2)) were detected in cerebral regions subtended by the ipsilateral carotid artery in eight cases and by the contralateral carotid artery in one case. In the stroke patient, 12 ischemic foci (maximum area 84.5 mm(2)) were exclusively located in the contralateral hemisphere. Follow-up MRI at 4.1 months (median, n = 7) identified residuals of cerebral ischemia only in this patient. CONCLUSIONS: Neuroprotected CAS is associated in about 25% of cases with predominantly silent cerebral ischemia. Our findings suggest manipulation of endoluminal equipment in the supraaortic vessels to be a major risk factor for cerebral embolism during neuroprotected CAS.

Feasibility and efficacy of balloon-based neuroprotection during carotid artery stenting in a single-center setting.

We sought to prospectively assess the feasibility and in-hospital efficacy of the PercuSurge GuardWire temporary balloon-occlusive system for neuroprotection during carotid angioplasty and stenting (CAS).Carotid angioplasty and stenting harbors a risk of distal embolization. Cerebral protection devices are currently under clinical investigation.Ninety-six consecutive patients with carotid bifurcation disease underwent a total of 102 CAS procedures with the intention to use the GuardWire for neuroprotection. GuardWire deployment was achieved in 99 procedures performed in 93 patients (97%). Device failure (n = 3) and severe neurologic responses to balloon occlusion of the targeted carotid artery (n = 2) accounted for five additional procedures that were essentially concluded without neuroprotection, for a total of 94 procedures completed as intended in 88 patients (92% procedural feasibility rate). Carotid angioplasty and stenting was performed successfully in 94 patients (100 procedures). There were no in-hospital deaths; but three patients (3.1%) sustained strokes, and two patients experienced transient ischemic attacks, for a total periprocedural complication rate of 5.2%. One major stroke occurred with the GuardWire in place, whereas two minor strokes were observed in patients in whom the device could not be deployed. Thus, successful neuroprotected CAS without major neurologic events was achieved in 87 patients (91%). The GuardWire temporary balloon-occlusive system is feasible as an adjunct to CAS in the majority of patients. It is associated with a 3.1% rate of major periprocedural neurologic complications. Adverse neurologic reactions to balloon occlusion may prohibit effective use of the system in about 2% of patients.

Beyond the early stages: insights from the ASSURE registry on bioresorbable vascular scaffolds.

AIMS: Bioresorbable vascular scaffolds (BVS) have been available on the European market since November 2011. The ASSURE registry aims to investigate the safety and efficacy of the Absorb everolimus-eluting bioresorbable vascular scaffold in a real-world setting. METHODS AND RESULTS: Patients with de novo coronary artery disease were consecutively enrolled at six German centres in this prospective registry. Outcomes were procedural success, cardiovascular death, myocardial infarction, and ischaemia-driven target lesion revascularisation (TLR). Angiographic parameters were assessed quantitatively and visual estimates of lesion dimensions were studied. One hundred and eighty-three patients were treated. In 128 (64.7%) lesions a complex ACC/AHA morphology was present. Procedural success was achieved in all patients. Acute gain was 1.54±0.51 mm, resulting in a final minimal lumen diameter (MLD), which met the baseline reference vessel diameter (RVD), although visual estimates overrated the RVD by 0.5±0.5 mm. Up to 12 months, one patient (0.5%) had died from gastrointestinal bleeding, three (1.7%) non-target vessel myocardial infarctions occurred, and five (2.8%) TLR had become necessary because of restenosis. CONCLUSIONS: One-year results suggest that bioresorbable vascular scaffolds for de novo coronary artery disease are associated with favourable clinical and functional outcomes in routine clinical practice despite a visually overestimated RVD.

Coronary plaque composition, morphology, and outcomes in patients with and without chronic kidney disease presenting with acute coronary syndromes.

OBJECTIVES: This study sought to evaluate the impact of chronic kidney disease (CKD) on coronary atherosclerotic plaque composition, morphology, and outcomes in patients with acute coronary syndromes (ACS). BACKGROUND: CKD patients presenting with ACS are at increased risk for adverse events. Whether or not this increased risk reflects differences in coronary plaque composition remains unknown. METHODS: In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, patients presenting with ACS in whom percutaneous coronary intervention was successful underwent 3-vessel grayscale and radiofrequency intravascular ultrasound imaging. Lesions were prospectively characterized, and patients were followed for a median of 3.4 years. We conducted a patient-level and lesion-level analysis of study participants by comparing intravascular ultrasound parameters of untreated nonculprit lesions in patients with and without CKD. RESULTS: Patients with CKD (n = 73, 11.3%) were older, more often female and diabetic compared to those without CKD (n = 573). Nonculprit lesions in patients with (n = 280) versus without (n = 2,390) CKD were more likely to have plaque burden ≥ 70% (11.8% vs. 8.5%, p = 0.05) and minimal luminal area ≤ 4.0 mm(2) (25.9% vs. 19.2%, p = 0.005). The percentage of plaque comprised of necrotic core (15.0% vs. 13.0%, p = 0.0001) and dense calcium (8.2% vs. 6.4%, p < 0.0001) was higher while fibrous tissue (57.7% vs. 59.8%, p < 0.0001) was lower in CKD versus non-CKD lesions. The 3-year composite rate of cardiac death, cardiac arrest, or myocardial infarction (15.1% vs. 3.3%, p < 0.0001) was significantly higher in patients with than in those without CKD, although there were no differences in the rates of events adjudicated to nonculprit lesions. CONCLUSIONS: Following percutaneous coronary intervention of all culprit lesions in ACS, patients with versus without CKD have more extensive and severe atherosclerosis remaining in their coronary tree with plaque composed of greater necrotic core and less fibrous tissue. These influences resulted in nonsignificantly different rates of non-culprit lesion-related adverse events, although cardiac death, arrest, or myocardial infarction were more common in patients with CKD.

Treatment of bifurcation lesions with a drug-eluting balloon: the PEPCAD V (Paclitaxel Eluting PTCA Balloon in Coronary Artery Disease) trial.

AIMS: Percutaneous coronary interventions for bifurcation lesions are often complex and associated with an unsatisfactory result. The aim of this first-in-man, observational study was to investigate the efficacy and safety of a paclitaxel-eluting balloon in these lesions. METHODS AND RESULTS: Twenty-eight patients presenting significant coronary bifurcational lesions of the left coronary artery were studied. The main branch (MB) and the side branch (SB) were dilated with a drug-eluting balloon (DEB; SeQuent Please balloon catheter , 3 µg paclitaxel/mm2 balloon surface). An open-cell bare-metal stent (BMS; Coroflex) was then deployed in the MB. Only if the SB had a TIMI flow

Clinical outcome 2 years after intracoronary administration of bone marrow-derived progenitor cells in acute myocardial infarction.

BACKGROUND: The aim of this study was to investigate the clinical outcome 2 years after intracoronary administration of autologous progenitor cells in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: Using a double-blind, placebo-controlled, multicenter trial design, we randomized 204 patients with successfully reperfused AMI to receive intracoronary infusion of bone marrow-derived progenitor cells (BMC) or placebo medium into the infarct artery 3 to 7 days after successful infarct reperfusion therapy. At 2 years, the cumulative end point of death, myocardial infarction, or necessity for revascularization was significantly reduced in the BMC group compared with placebo (hazard ratio, 0.58; 95% CI, 0.36 to 0.94; P=0.025). Likewise, the combined end point death and recurrence of myocardial infarction and rehospitalization for heart failure, reflecting progression toward heart failure, was significantly reduced in the BMC group (hazard ratio, 0.26; 95% CI, 0.085 to 0.77; P=0.015). Intracoronary administration of BMC remained a significant predictor of a favorable clinical outcome by Cox regression analysis when adjusted for classical predictors of poor outcome after AMI. There was no evidence of increased restenosis or atherosclerotic disease progression after BMC therapy nor any evidence of increased ventricular arrhythmias or neoplasms. In addition, regional left ventricular contractility of infarcted segments, as assessed by MRI in a subgroup of patients at 2-year follow-up, was significantly higher in the BMC group compared with the placebo group (P<0.001). CONCLUSIONS: Intracoronary administration of BMC is associated with a significant reduction of the occurrence of major adverse cardiovascular events maintained for 2 years after AMI. Moreover, functional improvements after BMC therapy may persist for at least 2 years. Larger studies focusing on clinical event rates are warranted to confirm the effects of BMC administration on mortality and progression of heart failure in patients with AMIs. Clinical Trial Registration- clinicaltrials.gov. Identifier: NCT00279175.

Intracoronary infusion of bone marrow-derived mononuclear cells abrogates adverse left ventricular remodelling post-acute myocardial infarction: insights from the reinfusion of enriched progenitor cells and infarct remodelling in acute myocardial infarction (REPAIR-AMI) trial.

AIMS: Depressed left ventricular ejection fraction (LVEF) despite successful reperfusion therapy is the single most powerful predictor of progressive LV enlargement after acute myocardial infarction (AMI) and independently determines adverse outcome in these patients. METHODS AND RESULTS: We investigated the effect of intracoronary administration of bone marrow-derived mononuclear cells (BMC) within 7 days after successful reperfusion therapy for AMI, on early (within 4 months) LV remodelling processes assessed by quantitative LV angiography. Overall, 95 patients received BMC and 92 patients received placebo. Remodelling was assessed as the changes in either LVEF and end-systolic volume (ESV) or stroke volume and end-diastolic volume (EDV) at 4 months, respectively. Baseline LVEF was inversely correlated with ESV expansion at 4 months in the placebo group, but not in the BMC group. Likewise, EDV expansion was significantly correlated with baseline LVEF in the placebo (r = -0.36, P < 0.001), but not in the BMC group (r = -0.17, P = 1.0). Analysing the interaction between convalescent LV contractile function and LV volumes revealed that the increase in LVEF or stroke volume did not occur at the expense of increases in ESV or EDV, respectively, in the BMC group. CONCLUSION: Intracoronary administration of BMC eliminates the correlation between depressed LVEF after reperfusion therapy and LV expansion during follow-up and, thereby, abrogates early LV remodelling after AMI.

Supported high-risk percutaneous coronary intervention with the Impella 2.5 device the Europella registry.

OBJECTIVES: This retrospective multicenter registry evaluated the safety and feasibility of left ventricular (LV) support with the Impella 2.5 (Abiomed Europe GmbH, Aachen, Germany) during high-risk percutaneous coronary intervention (PCI). BACKGROUND: Patients with complex or high-risk coronary lesions, such as last remaining vessel or left main lesions, are increasingly being treated with PCI. Because periprocedural hemodynamic compromise and complications might occur rapidly, many of these high-risk procedures are being performed with mechanical cardiac assistance, particularly in patients with poor LV function. The Impella 2.5, a percutaneous implantable LV assist device, might be a superior alternative to the traditionally used intra-aortic balloon pump. METHODS: The Europella registry included 144 consecutive patients who underwent a high-risk PCI. Safety and feasibility end points included incidence of 30-day adverse events and successful device function. RESULTS: Patients were older (62% >70 years of age), 54% had an LV ejection fraction < or = 30%, and the prevalence of comorbid conditions was high. Mean European System for Cardiac Operative Risk Evaluation score was 8.2 (SD 3.4), and 43% of the patients were refused for coronary artery bypass grafting. A PCI was considered high-risk due to left main disease, last remaining vessel disease, multivessel coronary artery disease, and low LV function in 53%, 17%, 81%, and 35% of the cases, respectively. Mortality at 30 days was 5.5%. Rates of myocardial infarction, stroke, bleeding requiring transfusion/surgery, and vascular complications at 30 days were 0%, 0.7%, 6.2%, and 4.0%, respectively. CONCLUSIONS: This large multicenter registry supports the safety, feasibility, and potential usefulness of hemodynamic support with Impella 2.5 in high-risk PCI.

Improved clinical outcome after intracoronary administration of bone-marrow-derived progenitor cells in acute myocardial infarction: final 1-year results of the REPAIR-AMI trial.

AIMS: To investigate the clinical outcome after intracoronary administration of autologous progenitor cells in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: Using a double-blind, placebo-controlled multicentre trial design, we randomized 204 patients with successfully reperfused AMI to receive intracoronary infusion of bone-marrow-derived progenitor cells (BMCs) or placebo medium into the infarct artery 3-7 days after successful infarct reperfusion therapy. At 12 months, the pre-specified cumulative endpoint of death, myocardial infarction, or necessity for revascularization was significantly reduced in the BMC group compared with placebo (P=0.009). Likewise, the combined endpoint death, recurrence of myocardial infarction, and rehospitalization for heart failure was significantly (P=0.006) reduced in patients receiving intracoronary BMC administration. Intracoronary administration of BMC remained a significant predictor of a favourable clinical outcome by Cox regression analysis, adjusting for classical predictors of poor outcome after AMI. CONCLUSION: Intracoronary administration of BMCs is associated with a significant reduction of the occurrence of major adverse cardiovascular events after AMI. Large-scale studies are warranted to confirm the effects of BMC administration on mortality and morbidity in patients with AMIs.

Angiographic and clinical outcomes at 8 months of cutting balloon angioplasty and beta-brachytherapy for native vessel in-stent restenosis (BETACUT): results from a stopped randomized controlled trial.

The objective of this study was to assess angiographic and clinical outcomes of cutting balloon (CB) angioplasty and concomitant Sr/Y-90 beta-brachytherapy as a treatment modality for patients with native vessel in-stent restenosis (ISR). Procedural advantages over the standard balloon (SB) have been claimed for the CB. Intracoronary brachytherapy preceded by SB angioplasty is regarded as the treatment of choice in patients with ISR. In an interim analysis of a prospective randomized trial designed for 652 patients, 100 consecutive patients with ISR were assigned to treatment with SB angioplasty (n = 51) or CB angioplasty (n = 49), followed in either case by Sr/Y-90 beta-brachytherapy. Quantitative coronary angiography at baseline, postintervention, and at 8 months was performed by an independent central laboratory. More than 90% of target lesions in the overall patient population were diffuse, with 14% of stents totally occluded. Procedural parameters and immediate angiographic outcomes were essentially the same in either study arm. At 8 months, no statistically significant differences were observed in recurrent angiographic restenosis (SB = 26.1%; CB = 29.5%; P = 0.82), target lesion revascularizations (SB = 13.7%; CB = 8.2%; P = 0.53), and major adverse cardiac events (SB = 15.7%; CB = 8.2%; P = 0.36). In this interim analysis, there was no indication of a beneficial effect of CB use over SB use in terms of angiographic or clinical outcomes at 8-month follow-up. CB angioplasty appears to be as safe and efficacious as SB angioplasty in beta-radiation treatment of patients with predominantly diffuse native vessel ISR. It was decided to discontinue the trial.

Angiographic outcome after intracoronary X-Sizer helical atherectomy and thrombectomy: first use in humans.

The objective of this study was to evaluate the early angiographic outcome in the first human subjects who underwent intracoronary atherectomy and thrombectomy using the X-Sizer helical cutting and aspiration system. Percutaneous coronary interventions in patients with thrombo-occlusive disease or friable degenerative saphenous vein grafts are associated with considerable periprocedural morbidity and mortality, predominantly related to microscopic distal embolization. X-Sizer catheter system is a novel atherectomy and thrombectomy device that consists of a helix cutter connected to a handheld motor drive unit and a vacuum collection chamber for aspiration of excised atheroma, thrombus, and debris. Quantitative coronary angiography was obtained in 14 patients before and after X-Sizer extraction atherectomy with adjunctive balloon angioplasty and stenting. Thirteen native coronary arteries and one saphenous vein graft were treated. Mean preprocedural reference vessel diameter was 3.06 +/- 0.66 mm. There were 71.4% AHA/ACC type B2 and C lesions. Preprocedural thrombus was present in nine patients and total occlusion in 64% of cases. Minimal luminal diameter was increased from 0.29 +/- 0.47 mm to 1.32 +/- 0.64 mm, a gain of 1.04 +/- 0.69 mm after atherectomy. Final total gain was 1.47 +/- 0.61 mm. Mean diameter stenosis was reduced from 89.3% to a final residual stenosis of 14.4%. Postatherectomy distal embolization occurred in one patient who had heavy preprocedural thrombus burden. No episodes of perforation, distal coronary spasm, abrupt closure, or slow/no-reflow occurred. The angiographic analysis of the first cohort of human subjects suggests that X-Sizer helical atherectomy is a feasible method of removing occlusive tissue or thrombus in coronary artery disease with a low angiographic complication rate. A large-scale randomized phase II clinical trial is underway to determine the ultimate safety and efficacy of this device in thrombo-occlusive native coronary arteries and saphenous vein grafts.