Joseph Dens

Apical ballooning of the left ventricle: first series in white patients

Background: A cardiac syndrome of “apical ballooning” was recently described, consisting of an acute onset of transient extensive akinesia of the apical and mid portions of the left ventricle, without significant stenosis on the coronary angiogram, accompanied by chest symptoms, ECG changes, and a limited release of cardiac markers disproportionate to the extent of akinesia. Until now, this syndrome has been reported only in Japanese patients. Objective: To describe 13 white patients who presented with this syndrome over the previous four years. Results: All but one of the patients were women with a mean age of 62 years. Eight of them presented with chest pain, of whom six had cardiogenic shock. In nine patients a triggering factor was identified: emotional stress in three, trauma in one, pneumonia in one, asthma crisis in one, exercise in two, and cerebrovascular accident in one. In all patients left ventriculography showed very extensive apical akinesia (“apical ballooning”) in the absence of a significant coronary artery stenosis, not corresponding with the perfusion territory of a single epicardial coronary artery. Mean maximal creatine kinase MB and troponin rise were 27.4 μg/l (range 5.2–115.7 μg/l, median 16.6 μg/l) and 18.7 μg/l (range 2.0–97.6 μg/l, median 14.5 μg/l), respectively. Six patients were treated with intra-aortic balloon counterpulsation. One patient died of multiple organ failure. On necropsy, no myocardial infarction was found. In the 12 survivors, left ventricular systolic function recovered completely within three weeks. Conclusions: This is the first series of “apical ballooning” to be reported in white patients. Despite dramatic initial presentation, left ventricle function recovered completely within three weeks in the survivors.

A Prospective, Randomized Evaluation of a Novel Everolimus-Eluting Coronary Stent : The PLATINUM (A Prospective, Randomized, Multicenter Trial to Assess an Everolimus-Eluting Coronary Stent System [PROMUS Element] for the Treatment of up to Two De Novo Coronary Artery Lesions) Trial

OBJECTIVES We sought to evaluate the clinical outcomes with a novel platinum chromium everolimus-eluting stent (PtCr-EES) compared with a predicate cobalt chromium everolimus-eluting stent (CoCr-EES) in patients undergoing percutaneous coronary intervention (PCI). BACKGROUND Randomized trials have demonstrated an excellent safety and efficacy profile for the CoCr-EES. The PtCr-EES uses the identical antiproliferative agent and polymer but with a novel platinum chromium scaffold designed for enhanced deliverability, vessel conformability, side-branch access, radiopacity, radial strength, and fracture resistance. METHODS A total of 1,530 patients undergoing PCI of 1 or 2 de novo native lesions were randomized at 132 worldwide sites to CoCr-EES (n = 762) or PtCr-EES (n = 768). The primary endpoint was the 12-month rate of target lesion failure (TLF), the composite of target vessel-related cardiac death, target vessel-related myocardial infarction (MI), or ischemia-driven target lesion revascularization (TLR) in the per-protocol population (patients who received ≥1 assigned study stent), powered for noninferiority. RESULTS The 12-month rate of TLF in the per-protocol population occurred in 2.9% versus 3.4% of patients assigned to CoCr-EES versus PtCr-EES, respectively (difference: 0.5%, 95% confidence interval: -1.3% to 2.3%, p(noninferiority) = 0.001, p(superiority) = 0.60). By intention-to-treat, there were no significant differences between CoCr-EES and PtCr-EES in the 12-month rates of TLF (3.2% vs. 3.5%, p = 0.72), cardiac death or MI (2.5% vs. 2.0%, p = 0.56), TLR (1.9% vs. 1.9%, p = 0.96), or Academic Research Consortium definite or probable stent thrombosis (0.4% vs. 0.4%, p = 1.00). CONCLUSIONS In this large-scale, prospective, single-blind randomized trial, a novel PtCr-EES was noninferior to the predicate CoCr-EES for TLF, with nonsignificant differences in measures of safety and efficacy through 12-month follow-up after PCI.

Primary endpoint results of the EVOLVE trial: a randomized evaluation of a novel bioabsorbable polymer-coated, everolimus-eluting coronary stent.

OBJECTIVES This study sought to compare the safety and efficacy of 2 dose formulations of SYNERGY, a novel bioabsorbable polymer everolimus-eluting stent (EES) (Boston Scientific Corp., Natick, Massachusetts) compared with the durable polymer PROMUS Element EES (Boston Scientific Corp.). BACKGROUND Durable polymer coatings on drug-eluting stents have been associated with chronic inflammation and impaired healing. Bioabsorbable polymer-coated drug-delivery systems may reduce the risk of late adverse events, including stent thrombosis, and thus the need for prolonged dual-antiplatelet therapy. METHODS A total of 291 patients with a de novo lesion ≤28 mm in length, in a coronary artery of ≥2.25 to ≤3.5 mm diameter, were enrolled in the EVOLVE study, a prospective, randomized, single-blind, noninferiority trial. Patients were randomly assigned in a 1:1:1 ratio to PROMUS Element, SYNERGY, or SYNERGY half dose. The primary clinical endpoint was the 30-day rate of target lesion failure, defined as cardiac death or myocardial infarction related to the target vessel, or target lesion revascularization. The primary angiographic endpoint was 6-month in-stent late loss measured by quantitative coronary angiography. RESULTS The 30-day primary clinical endpoint of target lesion failure occurred in 0%, 1.1%, and 3.1% of patients in the PROMUS Element, SYNERGY, and SYNERGY half dose groups, respectively. The 6-month in-stent late loss was 0.15 ± 0.34 mm for PROMUS Element, 0.10 ± 0.25 mm for SYNERGY, and 0.13 ± 0.26 mm for SYNERGY half dose (SYNERGY, difference -0.06, upper 95.2% confidence limit: 0.02, p for noninferiority <0.001; SYNERGY half dose, difference -0.03, upper 95.2% confidence limit: 0.05, p for noninferiority <0.001). Clinical event rates remained low and comparable between groups, with no stent thromboses in any group at 6 months. CONCLUSIONS The EVOLVE trial confirms the effective delivery of everolimus by a unique directional bioabsorbable polymer system utilizing the SYNERGY stent. (A Prospective Randomized Multicenter Single-Blind Noninferiority Trial to Assess the Safety and Performance of the Evolution Everolimus-Eluting Monorail Coronary Stent System [Evolution Stent System] for the Treatment of a De Novo Atherosclerotic Lesion [EVOLVE]; NCT01135225).

9-Month Clinical, Angiographic, and Intravascular Ultrasound Results of a Prospective Evaluation of the Axxess Self-Expanding Biolimus A9-Eluting Stent in Coronary Bifurcation Lesions : The DIVERGE (Drug-Eluting Stent Intervention for Treating Side Branches Effectively) Study

OBJECTIVES This study sought to assess the safety and performance of the Axxess (Devax Inc., Lake Forest, California) self-expanding drug-eluting stent in coronary bifurcation lesions. BACKGROUND Percutaneous treatment of coronary bifurcations is a predictor of adverse late outcomes, in part because of the lack of dedicated devices. METHODS Patients with de novo bifurcation lesions were prospectively enrolled in a multicenter study. The Axxess stent was deployed at the level of the carina followed by additional sirolimus-eluting stents in the distal parent vessel (PV) and/or side branch (SB). All patients underwent clinical follow-up at 9 months; 150 were to receive control angiography and 76 were to receive intravascular ultrasound. The primary end point was the rate of major adverse cardiac events (MACE): a composite of death, myocardial infarction (MI), and target lesion revascularization (TLR). Secondary end points included in-segment restenosis, late loss, and percent neointimal volume obstruction. RESULTS Overall, 302 patients were treated with 299 Axxess stents (99%). Additional stenting of 1 branch was performed in 21.7% of patients (17.7% PV, 4% SB), and of both branches in 64.7%. At 9 months, 99.3% of patients returned for clinical follow-up; from the angiographic and IVUS substudies, 93.3% and 89.4% returned. The cumulative 9-month MACE rate was 7.7% (0.7% death, 3.3% non-Q-wave MI, 1.0% Q-wave MI, 4.3% TLR). Subacute and late stent thrombosis occurred in 0.7% and 0.3% of patients. Total restenosis was 6.4% (3.6% PV, 4.3% SB), late loss was 0.20 +/- 0.41 mm in the PV and 0.17 +/- 0.34 mm in the SB. In the Axxess stent segment, percent neointimal volume obstruction was 4.3 +/- 5.2%. CONCLUSIONS This prospective multicenter study confirms the safety and performance of the Axxess stent in bifurcation lesions. (Drug-Eluting Stent Intervention for Treating Side Branches Effectively; ACTRN12606000259549).

Study of antirestenosis with the BiodivYsio dexamethasone-eluting stent (STRIDE): A first-in-human multicenter pilot trial

The aim of this multicenter pilot study was to evaluate the acute safety and efficacy of the dexamethasone‐eluting stent (0.5 μg/mm2 of stent) implanted in patients with de novo single‐vessel disease. This study included 71 patients, 42% of whom had unstable angina pectoris. An appropriately sized BiodivYsio Matrix Lo stent loaded with a total dexamethasone dose of 0.5 μg/mm2 of stent was used. Technical device success rate was 95%. Six‐month MACE occurred in two patients (3.3%). Binary restenosis rate was 13.3%. Late loss was 0.45. Late loss and percent diameter stenosis were lower in the unstable angina pectoris patients compared to the stable patients (0.32 ± 0.39 vs. 0.60 ± 0.55 mm, P < 0.07, and 26.86 ± 14 vs. 38.40 ± 16%, P < 0.02). This study demonstrated the feasibility and safety of the implantation of a dexamethasone‐eluting stent and its effect on in‐stent neointimal hyperplasia. Catheter Cardiovasc Interv 2003;60:172–178.

Six-Month Results of the NEVO RES-ELUTION I (NEVO RES-I) Trial A Randomized, Multicenter Comparison of the NEVO Sirolimus-Eluting Coronary Stent With the TAXUS Liberté Paclitaxel-Eluting Stent in De Novo Native Coronary Artery Lesions

Background—Drug-eluting stents reduce restenosis and reintervention rates but are complicated by stent thrombosis, which may be related to polymer coating. The NEVO sirolimus-eluting coronary stent (NEVO SES) is designed to improve long-term percutaneous coronary intervention safety by combining sirolimus release from reservoirs with bioabsorbable polymer to reduce spatial and temporal polymer exposure. Methods and Results—NEVO ResElution-I was a prospective randomized study in 394 patients with coronary artery disease comparing the NEVO SES with the TAXUS Liberté paclitaxel-eluting coronary stent (TAXUS Liberté PES) stent. The primary end point was in-stent angiographic late loss at 6 months. Six months after percutaneous coronary intervention (PCI), the primary end point favored NEVO SES (0.13±0.31 mm versus 0.36±0.48 mm, P<0.001 for noninferiority and superiority). The study was not powered for clinical end points and showed no significant difference for NEVO SES versus TAXUS Liberté PES: death: 0.5 versus 1.6%, P=0.36; myocardial infarction: 2.0 versus 2.6%, P=0.75; target lesion revascularization: 1.5 versus 3.2%, P=0.33; major adverse cardiac events: 4.0 versus 7.4%, P=0.19. No stent thrombosis was observed with NEVO SES, whereas 2 cases occurred in TAXUS Liberté PES. Intravascular ultrasound showed lower percent volume obstruction for NEVO SES (5.5±11% versus 11.5±9.7%, P=0.016). Conclusions—This trial proved the superiority of NEVO SES over TAXUS Liberté PES for the primary angiographic end point of in-stent late loss. No stent thrombosis occurred in the NEVO SES group. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00606333.Background— Drug-eluting stents reduce restenosis and reintervention rates but are complicated by stent thrombosis, which may be related to polymer coating. The NEVO sirolimus-eluting coronary stent (NEVO SES) is designed to improve long-term percutaneous coronary intervention safety by combining sirolimus release from reservoirs with bioabsorbable polymer to reduce spatial and temporal polymer exposure. Methods and Results— NEVO ResElution-I was a prospective randomized study in 394 patients with coronary artery disease comparing the NEVO SES with the TAXUS Liberte paclitaxel-eluting coronary stent (TAXUS Liberte PES) stent. The primary end point was in-stent angiographic late loss at 6 months. Six months after percutaneous coronary intervention (PCI), the primary end point favored NEVO SES (0.13±0.31 mm versus 0.36±0.48 mm, P <0.001 for noninferiority and superiority). The study was not powered for clinical end points and showed no significant difference for NEVO SES versus TAXUS Liberte PES: death: 0.5 versus 1.6%, P =0.36; myocardial infarction: 2.0 versus 2.6%, P =0.75; target lesion revascularization: 1.5 versus 3.2%, P =0.33; major adverse cardiac events: 4.0 versus 7.4%, P =0.19. No stent thrombosis was observed with NEVO SES, whereas 2 cases occurred in TAXUS Liberte PES. Intravascular ultrasound showed lower percent volume obstruction for NEVO SES (5.5±11% versus 11.5±9.7%, P =0.016). Conclusions— This trial proved the superiority of NEVO SES over TAXUS Liberte PES for the primary angiographic end point of in-stent late loss. No stent thrombosis occurred in the NEVO SES group. Clinical Trial Registration— URL: . Unique identifier: [NCT00606333][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00606333&atom=%2Fcirccvint%2F3%2F6%2F556.atom

Long term effects of nisoldipine on the progression of coronary atherosclerosis and the occurrence of clinical events: the NICOLE study

Background: Earlier angiographic studies have suggested that calcium antagonists may prevent the formation of new coronary lesions and the progression of minimal lesions. Conversely, a meta-analysis suggested that these drugs may increase cardiovascular mortality and morbidity in patients with coronary heart disease. Objective: To investigate whether nisoldipine retards the progression of coronary atherosclerosis or reduces the occurrence of clinical events. Design and setting: The NICOLE study (NIsoldipine in COronary artery disease in LEuven) is a single centre, randomised, double blind, placebo controlled trial with coronary angiography at baseline, six months, and three years of follow up. Patients: 826 patients who had undergone successful coronary angioplasty were randomised to nisoldipine 40 mg once daily or placebo. The intention to treat and per protocol population consisted of 819 and 578 patients, respectively. Results: In the per protocol population, 625 of the nisoldipine treated and 655 of the placebo treated patients (NS) showed angiographic progression in at least one coronary arterial segment, defined as an increase in diameter stenosis of ≥ 13%. The average minimum luminal diameter of the non-dilated lesions decreased by 0.163 mm and 0.167 mm in the nisoldipine and placebo groups, respectively (NS). The respective numbers of new lesions detected were 7 and 13 (NS). In the intention to treat population, the rates of death, stroke, and acute myocardial infarction were similar in both treatment groups. However, nisoldipine use was associated with fewer revascularisation procedures and thus the percentage of patients with any clinical event was lower (44.6% v 52.6%, p = 0.02). Conclusions: Nisoldipine has no demonstrable effect on the angiographic progression of coronary atherosclerosis or the risk of major cardiovascular events but its use is associated with fewer revascularisation procedures.

Myths to Debunk to Improve Management, Referral, and Outcomes in Patients With Chronic Total Occlusion of an Epicardial Coronary Artery.

A chronic total occlusion (CTO) is defined as an occlusive (100% stenosis) coronary lesion with anterograde Thrombolysis In Myocardial Infarction 0 flow for at least 3 months. CTOs are common in patients referred for coronary angiography (up to 33%) and are associated with angina, impaired quality of life, and reduced survival. Unfortunately, CTO percutaneous coronary intervention continues to be underperformed worldwide (10% to 15% at most institutions, ∼30% where expert operators are available). The aim of this study was to address common fallacies pertaining to CTOs among cardiologists by providing a concise review of pertinent previously published reports along with an update on safety and efficacy of state-of-the-art CTO percutaneous coronary intervention techniques.

Analysis of left main coronary artery bifurcation lesions treated with biolimus‐eluting DEVAX AXXESS plus nitinol self‐expanding stent: Intravascular ultrasound results of the AXXENT trial

Objective: To assess the efficacy of the AXXESS stent on the treatment of left main coronary artery (LMCA) bifurcation lesions using IVUS. Background: The treatment of LMCA bifurcation lesions remains challenging even with the use of drug‐eluting stents. The AXXESS system is a biolimus A9‐eluting self‐expanding stent, dedicated to the treatment of bifurcation lesions. Methods: Data were obtained from the AXXENT trial, a prospective, single‐arm, multicenter study designed to evaluate the efficacy of the AXXESS stent on the treatment of LMCA bifurcation lesions. IVUS was available in 26 cases at 6‐months follow‐up. Volumetric and cross‐sectional analyses within the AXXESS stent, and cross‐sectional analyses at the ostia of left anterior descending (LAD) and left circumflex coronary arteries (LCX) were performed. Results: Within the AXXESS stent, percent neointimal volume obstruction was (3.0 ± 4.1)% with a minimal lumen area of 10.3 ± 2.6 mm2. AXXESS stent volume showed an 12.4% increase at follow‐up compared with postprocedure (P = 0.04). Lumen area was significantly smaller in the LCX ostium compared with the LAD ostium at follow‐up (3.6 ± 1.3 mm2 vs. 5.5 ± 2.0 mm2, P = 0.0112). There was greater neointimal formation in the LCX ostium compared with the LAD ostium (1.37 ± 1.20 mm2 vs. 0.30 ± 0.36 mm2, P = 0.0003). Conclusions: The AXXESS stent in the LMCA showed enlargement through 6‐months follow‐up and significant neointimal suppression. Greater neointimal formation and relatively inadequate stent expansion may contribute to luminal narrowing in the LCX ostium.

The GENESIS (Randomized, Multicenter Study of the Pimecrolimus-Eluting and Pimecrolimus/Paclitaxel-Eluting Coronary Stent System in Patients with De Novo Lesions of the Native Coronary Arteries) Trial

OBJECTIVES The aim of this study was to compare, in a randomized multicenter trial, paclitaxel-eluting stents (CoStar, Conor Medsystems, Menlo Park, California) versus pimecrolimus-eluting stents (Corio, Conor Medsystems) versus stents with dual elution of both drugs (SymBio, Conor Medsystems) in native coronary arteries. BACKGROUND The CoStar cobalt-chromium reservoir-based stent platform, eluting paclitaxel in a controlled way via a bioresorbable polymer, reduces restenosis versus its respective bare-metal stent. The reservoir system allows the use of other drugs targeted to different mechanisms involved in the process of vascular restenosis and simultaneous loading of multiple, synergistic drugs. METHODS Patients with single de novo lesions were asymmetrically randomized to 1 of the 3 types of stent (1:2:2). Six-month coronary angiography was planned in all. The primary analysis was a noninferiority test for the primary end point of 6-month angiographic in-stent late lumen loss of Corio versus CoStar and SymBio versus CoStar. Secondary end points included binary angiographic restenosis and major adverse clinical events (cardiac death, myocardial infarction, target vessel revascularization). RESULTS The trial was prematurely suspended after 246 patients were enrolled (planned enrollment: 375 patients): 49 patients received CoStar, 97 received SymBio, and 100 received Corio. In-stent late loss was significantly reduced with CoStar versus either SymBio or Corio (0.58 +/- 0.58 mm vs. 0.96 +/- 0.73 mm and 0.58 +/- 0.58 mm vs. 1.40 +/- 0.67 mm, p < 0.001 for both comparisons). Binary in-stent restenosis rates were, 7.1%, 20%, and 40.9%, respectively (p < 0.001 for both comparisons); 6-month major adverse cardiac event rates were, 2.0%, 14.4%, and 39.0%, respectively (p < 0.001 for both comparisons). CONCLUSIONS Stents eluting pimecrolimus or the dual combination of pimecrolimus and paclitaxel failed to show angiographic noninferiority when compared with paclitaxel-eluting stents. (A Randomized, Multi-Center Study of the Pimecrolimus-Eluting and Pimecrolimus/Paclitaxel-Eluting Coronary Stent Systems; NCT00322569).