Ori Ben-Yehuda

Relationship Between Infarct Size and Outcomes Following Primary PCI: Patient-Level Analysis From 10 Randomized Trials.

BACKGROUNDnPrompt reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) reduces infarct size and improves survival. However, the intuitive link between infarct size and prognosis has not been convincingly demonstrated in the contemporary era.nnnOBJECTIVESnThis study sought to determine the strength of the relationship between infarct size assessed early after primary percutaneous coronary intervention (PCI) in STEMI and subsequent all-cause mortality, reinfarction, and hospitalization for heart failure.nnnMETHODSnWe performed a pooled patient-level analysis from 10 randomized primary PCI trials (total 2,632 patients) in which infarct size was assessed within 1 month after randomization by either cardiac magnetic resonance (CMR) imaging or technetium-99m sestamibi single-photon emission computed tomography (SPECT), with clinical follow-up for ≥ 6 months.nnnRESULTSnInfarct size was assessed by CMR in 1,889 patients (71.8%) and by SPECT in 743 patients (28.2%). Median (25th, 75th percentile) time to infarct size measurement was 4 days (3, 10 days) after STEMI. Median infarct size (% left ventricular myocardial mass) was 17.9% (8.0%, 29.8%), and median duration of clinical follow-up was 352 days (185, 371 days). The Kaplan-Meier estimated 1-year rates of all-cause mortality, reinfarction, and HF hospitalization were 2.2%, 2.5%, and 2.6%, respectively. A strong graded response was present between infarct size (per 5% increase) and subsequent mortality (Cox-adjusted hazard ratio: 1.19 [95% confidence interval: 1.18 to 1.20]; p < 0.0001) and hospitalization for heart failure (adjusted hazard ratio: 1.20 [95% confidence interval: 1.19 to 1.21]; p < 0.0001), independent of age, sex, diabetes, hypertension, hyperlipidemia, current smoking, left anterior descending versus non-left anterior descending infarct vessel, symptom-to-first device time, and baseline TIMI (Thrombolysis In Myocardial Infarction) flow 0/1 versus 2/3. Infarct size was not significantly related to subsequent reinfarction.nnnCONCLUSIONSnInfarct size, measured by CMR or technetium-99m sestamibi SPECT within 1 month after primary PCI, is strongly associated with all-cause mortality and hospitalization for HF within 1 year. Infarct size may, therefore, be useful as an endpoint in clinical trials and as an important prognostic measure when caring for patients with STEMI.

Optical coherence tomography compared with intravascular ultrasound and with angiography to guide coronary stent implantation (ILUMIEN III: OPTIMIZE PCI): a randomised controlled trial

BACKGROUNDnPercutaneous coronary intervention (PCI) is most commonly guided by angiography alone. Intravascular ultrasound (IVUS) guidance has been shown to reduce major adverse cardiovascular events (MACE) after PCI, principally by resulting in a larger postprocedure lumen than with angiographic guidance. Optical coherence tomography (OCT) provides higher resolution imaging than does IVUS, although findings from some studies suggest that it might lead to smaller luminal diameters after stent implantation. We sought to establish whether or not a novel OCT-based stent sizing strategy would result in a minimum stent area similar to or better than that achieved with IVUS guidance and better than that achieved with angiography guidance alone.nnnMETHODSnIn this randomised controlled trial, we recruited patients aged 18 years or older undergoing PCI from 29 hospitals in eight countries. Eligible patients had one or more target lesions located in a native coronary artery with a visually estimated reference vessel diameter of 2·25-3·50 mm and a length of less than 40 mm. We excluded patients with left main or ostial right coronary artery stenoses, bypass graft stenoses, chronic total occlusions, planned two-stent bifurcations, and in-stent restenosis. Participants were randomly assigned (1:1:1; with use of an interactive web-based system in block sizes of three, stratified by site) to OCT guidance, IVUS guidance, or angiography-guided stent implantation. We did OCT-guided PCI using a specific protocol to establish stent length, diameter, and expansion according to reference segment external elastic lamina measurements. All patients underwent final OCT imaging (operators in the IVUS and angiography groups were masked to the OCT images). The primary efficacy endpoint was post-PCI minimum stent area, measured by OCT at a masked independent core laboratory at completion of enrolment, in all randomly allocated participants who had primary outcome data. The primary safety endpoint was procedural MACE. We tested non-inferiority of OCT guidance to IVUS guidance (with a non-inferiority margin of 1·0 mm2), superiority of OCT guidance to angiography guidance, and superiority of OCT guidance to IVUS guidance, in a hierarchical manner. This trial is registered with ClinicalTrials.gov, number NCT02471586.nnnFINDINGSnBetween May 13, 2015, and April 5, 2016, we randomly allocated 450 patients (158 [35%] to OCT, 146 [32%] to IVUS, and 146 [32%] to angiography), with 415 final OCT acquisitions analysed for the primary endpoint (140 [34%] in the OCT group, 135 [33%] in the IVUS group, and 140 [34%] in the angiography group). The final median minimum stent area was 5·79 mm2 (IQR 4·54-7·34) with OCT guidance, 5·89 mm2 (4·67-7·80) with IVUS guidance, and 5·49 mm2 (4·39-6·59) with angiography guidance. OCT guidance was non-inferior to IVUS guidance (one-sided 97·5% lower CI -0·70 mm2; p=0·001), but not superior (p=0·42). OCT guidance was also not superior to angiography guidance (p=0·12). We noted procedural MACE in four (3%) of 158 patients in the OCT group, one (1%) of 146 in the IVUS group, and one (1%) of 146 in the angiography group (OCT vs IVUS p=0·37; OCT vs angiography p=0·37).nnnINTERPRETATIONnOCT-guided PCI using a specific reference segment external elastic lamina-based stent optimisation strategy was safe and resulted in similar minimum stent area to that of IVUS-guided PCI. These data warrant a large-scale randomised trial to establish whether or not OCT guidance results in superior clinical outcomes to angiography guidance.nnnFUNDINGnSt Jude Medical.

Comparison of Stent Expansion Guided by Optical Coherence Tomography Versus Intravascular Ultrasound: The ILUMIEN II Study (Observational Study of Optical Coherence Tomography [OCT] in Patients Undergoing Fractional Flow Reserve [FFR] and Percutaneous Coronary Intervention).

OBJECTIVESnThe present study sought to determine whether optical coherence tomography (OCT) guidance results in a degree of stent expansion comparable to that with intravascular ultrasound (IVUS) guidance.nnnBACKGROUNDnThe most important predictor of adverse outcomes (thrombosis and restenosis) after stent implantation with IVUS guidance is the degree of stent expansion achieved.nnnMETHODSnWe compared the relative degree of stent expansion (defined as the minimal stent area divided by the mean of the proximal and distal reference lumen areas) after OCT-guided stenting in patients in the ILUMIEN (Observational Study of Optical Coherence Tomography [OCT] in Patients Undergoing Fractional Flow Reserve [FFR] and Percutaneous Coronary Intervention) (Nxa0= 354) and IVUS-guided stenting in patients in the ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) study (Nxa0= 586). Stent expansion was examined in all 940 patients in a covariate-adjusted analysis as well as in 286 propensity-matched pairs (total N = 572).nnnRESULTSnIn the matched-pair analysis, the degree of stent expansion was not significantly different between OCT and IVUS guidance (median [first, third quartiles]xa0= 72.8% [63.3, 81.3] vs. 70.6% [62.3, 78.8], respectively, pxa0= 0.29). Similarly, after adjustment for baseline differences in the entire population, the degree of stent expansion was also not different between the 2 imaging modalities (pxa0= 0.84). Although a higher prevalence of post-PCI stent malapposition, tissue protrusion, and edge dissections was detected by OCT, the rates of major malapposition, tissue protrusion, and dissections were similar after OCT- and IVUS-guided stenting.nnnCONCLUSIONSnIn the present post-hoc analysis of 2 prospective studies, OCT and IVUS guidance resulted in a comparable degree of stent expansion. Randomized trials are warranted to compare the outcomes of OCT- and IVUS-guided coronary stent implantation.

Vascular and Metabolic Implications of Novel Targeted Cancer Therapies: Focus on Kinase Inhibitors

Novel targeted cancer therapies, especially kinase inhibitors, have revolutionized the treatment of many cancers and have dramatically improved the survival of several types of malignancies. Because kinases not only are important in cancer development and progression, but also play a critical role in the cardiovascular (CV) system and metabolic homeostasis, important CV and metabolic sequelae have been associated with several types of kinase inhibitors. This paper reviews the incidences and highlights potential mechanisms of vascular and metabolic perturbations associated with 3 classes of commonly used kinase inhibitors that target the vascular endothelial growth factor signaling pathway, the ABL kinase, and the phosphoinositide 3-kinase/AKT/mammalian target of rapamycin signaling pathway. We propose preventive, screening, monitoring, and management strategies for CV care of patients treated with these novel agents.

Transcatheter Mitral Annuloplasty in Chronic Functional Mitral Regurgitation: 6-Month Results With the Cardioband Percutaneous Mitral Repair System.

OBJECTIVESnThis study sought to show safety and efficacy of the Cardioband system during 6 months after treatment.nnnBACKGROUNDnCurrent surgical and medical treatment options for functional mitral regurgitation (FMR) are limited. The Cardioband system (Valtech Cardio, OrYehuda, Israel) is a novel transvenous, transseptal direct annuloplasty device.nnnMETHODSnThirty-one patients (71.8 ± 6.9 years of age; 83.9% male; EuroSCORE II: 8.6 ± 5.9) with moderate to severe FMR, symptomatic heart failure, and depressed left ventricular function (left ventricular ejection fraction 34 ± 11%) were prospectively enrolled.nnnRESULTSnProcedural success rate, defined as delivery of the entire device, was 100%. There were no periprocedural deaths (0%), and mortality rate at 1 month or prior to hospital discharge and at 7 months was 5% and 9.7% respectively. Cinching of the implanted Cardioband reduced the annular septolateral dimension by >30% from 3.7 ± 0.5 cm at baseline to 2.5 ± 0.4xa0cm after 1 month and to 2.4 ± 0.4 cm after 6 months, respectively (pxa0< 0.001). Percentage of patients withxa0FMRxa0≥3 was reduced from 77.4% to 10.7% 1 month after the procedure (pxa0< 0.001) and 13.6% (pxa0< 0.001) at 7xa0months. Percentage of patients with New York Heart Association functional class III/IV decreased from 95.5% to 18.2%xa0after 7 months (pxa0< 0.001); exercise capacity as assessed by 6-min walking test increased from 250 ± 107 m to 332xa0±xa0118 m (pxa0< 0.001) and quality of life (Minnesota Living With Heart Failure Questionnaire) was also significantly improved (pxa0< 0.001).nnnCONCLUSIONSnIn this feasibility trial in symptomatic patients with FMR, transcatheter mitral annuloplasty with thexa0Cardioband was effective in reducing MR and was associated with improvement in heart failure symptoms andxa0demonstrated a favorable safety profile. (Cardioband With Transfemoral Delivery System; NCT01841554).

Plaque Characterization to Inform the Prediction and Prevention of Periprocedural Myocardial Infarction During Percutaneous Coronary Intervention : The CANARY Trial (Coronary Assessment by Near-infrared of Atherosclerotic Rupture-prone Yellow)

OBJECTIVESnThis study sought to determine whether pre-percutaneous coronary intervention (PCI) plaque characterization using near-infrared spectroscopy identifies lipid-rich plaques at risk of periprocedural myonecrosis and whether these events may be prevented by the use of a distal protection filter during PCI.nnnBACKGROUNDnLipid-rich plaques may be prone to distal embolization and periprocedural myocardial infarction (MI) in patients undergoing PCI.nnnMETHODSnPatients undergoing stent implantation of a single native coronary lesion were enrolled in a multicenter, prospective trial. Near-infrared spectroscopy and intravascular ultrasound were performed at baseline, and lesions with a maximal lipid core burden index over any 4-mm length (maxLCBI4mm) ≥600 were randomized to PCI with versus without a distal protection filter. The primary endpoint was periprocedural MI, defined as troponin or a creatine kinase-myocardial band increase to 3 or more times the upper limit of normal.nnnRESULTSnEighty-five patients were enrolled at 9 U.S. sites. The median (interquartile range) maxLCBI4mm was 448.4 (274.8 to 654.4) pre-PCI and decreased to 156.0 (75.6 to 312.6) post-PCI (p < 0.0001). Periprocedural MI developed in 21 patients (24.7%). The maxLCBI4mm was higher in patients with versus without MI (481.5 [425.6 to 679.6] vs. 371.5 [228.9 to 611.6], p = 0.05). Among 31 randomized lesions with maxLCBI4mm ≥600, there was no difference in the rates of periprocedural MI with versus without the use of a distal protection filter (35.7% vs. 23.5%, respectively; relative risk: 1.52; 95% confidence interval: 0.50 to 4.60, p = 0.69).nnnCONCLUSIONSnPlaque characterization by near-infrared spectroscopy identifies lipid-rich lesions with an increased likelihood of periprocedural MI after stent implantation, presumably due to distal embolization. However, in this pilot randomized trial, the use of a distal protection filter did not prevent myonecrosis after PCI of lipid-rich plaques.

Evaluation of a fully bioresorbable vascular scaffold in patients with coronary artery disease: Design of and rationale for the ABSORB III randomized trial

BACKGROUNDnRandomized trials have demonstrated progressive improvements in clinical and angiographic measures of restenosis with technologic iterations from balloon angioplasty to bare-metal stents and subsequently to drug-eluting stents (DES). However, the permanent presence of a metal stent prevents coronary vasomotion, autoregulation, and adaptive coronary remodeling. The limitations imposed by a permanent metal implant may be overcome with a bioresorbable scaffold. ABSORB III is a large-scale, multicenter, randomized trial designed to support US premarket approval of the ABSORB BVS platform and is the first study with sufficient size to allow valid examination of the relative clinical outcomes between metallic DES and bioresorbable scaffold.nnnDESIGNnABSORB III (ClincalTrials.gov NCT01751906) will register approximately 2,262 patients and includes a lead-in phase (n = 50), the primary randomized analysis group (n = 2,000), an imaging cohort (n = 200), and a pharmacokinetic substudy (n = 12). In the primary analysis group, approximately 2,000 patients with up to 2 de novo native coronary artery lesions in separate epicardial vessels will be prospectively assigned in a 2:1 ratio to ABSORB BVS versus XIENCE everolimus-eluting stents (EES). The primary end point is target lesion failure (the composite of cardiac death, target vessel-related myocardial infarction, or ischemia-driven target lesion revascularization) at 1 year, powered for noninferiority of ABSORB BVS compared to XIENCE EES. Clinical follow-up will continue for 5 years. Enrollment has been completed, and the principal results will be available in the fall of 2015.nnnCONCLUSIONSnThe large-scale ABSORB III randomized trial will evaluate the safety and effectiveness of ABSORB BVS compared to XIENCE EES in the treatment of patients with coronary artery disease.

Effects of Ranolazine on Angina and Quality of Life After Percutaneous Coronary Intervention With Incomplete Revascularization: Results From the Ranolazine for Incomplete Vessel Revascularization (RIVER-PCI) Trial

Background— Angina often persists or returns in populations following percutaneous coronary intervention (PCI). We hypothesized that ranolazine would be effective in reducing angina and improving quality of life (QOL) in incomplete revascularization (ICR) post-PCI patients. Methods and Results— In RIVER-PCI, 2604 patients with a history of chronic angina who had ICR post-PCI were randomized 1:1 to oral ranolazine versus placebo; QOL analyses included 2389 randomized subjects. Angina and QOL questionnaires were collected at baseline and months 1, 6, and 12. Ranolazine patients were more likely than placebo to discontinue study drug by month 6 (20.4% versus 14.1%, P<0.001) and 12 (27.2% versus 21.3%, P<0.001). Following qualifying index PCI, the primary QOL outcome (Seattle Angina Questionnaire [SAQ] angina frequency score) improved markedly, but similarly, in the ranolazine and placebo groups, respectively, from baseline (67.3±24.5 versus 69.7±24.0, P=0.01) to month 1 (86.6±18.1 versus 85.8±18.5, P=0.27) and month 12 (88.4±17.8 versus 88.5±17.8, P=0.94). SAQ angina frequency repeated measures did not differ in adjusted analysis between groups post baseline (mean difference 1.0; 95% CI -0.2, 2.2; P=0.11). Improvement in SAQ angina frequency was observed with ranolazine at month 6 among diabetics (mean difference 3.3; 95% CI 0.6, 6.1; P=0.02) and those with more angina (baseline SAQ angina frequency ⩽60; mean difference 3.4; 95% CI 0.6, 6.2; P=0.02), but was not maintained at month 12. Conclusions— Despite ICR following PCI, there was no incremental benefit in angina or QOL measures by adding ranolazine in this angiographically-identified population. These measures markedly improved within 1 month of PCI and persisted up to 1 year in both treatment arms. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01442038.

Effect of Technique on Outcomes Following Bioresorbable Vascular Scaffold Implantation: Analysis From the ABSORB Trials

BACKGROUNDnProcedural technique may affect clinical outcomes after bioresorbable vascular scaffold (BVS) implantation. Prior studies suggesting such a relationship have not adjusted for baseline patient and lesion characteristics that may have influenced operator choice of technique and outcomes.nnnOBJECTIVESnThis study sought to determine whether target lesion failure (TLF) (cardiac death, target-vessel myocardial infarction, or ischemia-driven target lesion revascularization) and scaffold thrombosis (ScT) rates within 3xa0years of BVS implantation are affected by operator technique (vessel size selection and pre- and post-dilation parameters).nnnMETHODSnTLF and ScT rates were determined in 2,973 patients with 3,149 BVS-treated coronary artery lesions fromxa05xa0prospective studies (ABSORB II, ABSORB China, ABSORB Japan, ABSORB III, and ABSORB Extend). Outcomes through 3xa0years (and between 0 to 1 and 1 to 3 years) were assessed according to pre-specified definitions of optimal techniquexa0(pre-dilation, vessel sizing, and post-dilation). Multivariable analysis was used to adjust for differences in up toxa018 patient and lesion characteristics.nnnRESULTSnOptimal pre-dilation (balloon to core laboratory-derived reference vessel diameter ratioxa0≥1:1), vessel size selection (reference vessel diameterxa0≥2.25xa0mm andxa0≤3.75xa0mm), and post-dilation (with a noncompliant balloon atxa0≥18xa0atm and larger than the nominal scaffold diameter, but not by >0.5xa0mm larger) in all BVS-treated lesions were performed in 59.2%, 81.6%, and 12.4% of patients, respectively. BVS implantation in properly sized vessels was an independent predictor of freedom from TLF through 1 year (hazard ratio [HR]: 0.67; pxa0=xa00.01) and through 3 years (HR:xa00.72; pxa0=xa00.01), and of freedom from ScT through 1 year (HR: 0.36; pxa0=xa00.004). Aggressive pre-dilation was an independent predictor of freedom from ScT between 1 and 3 years (HR: 0.44; pxa0=xa00.03), and optimal post-dilation was anxa0independent predictor of freedom from TLF between 1 and 3 years (HR: 0.55; pxa0=xa00.05).nnnCONCLUSIONSnIn the present large-scale analysis from the major ABSORB studies, after multivariable adjustment for baseline patient and lesion characteristics, vessel sizing and operator technique were strongly associated with BVS-related outcomes during 3-year follow-up. (ABSORB II Randomized Controlled Trial [ABSORB II]; NCT01425281; ABSORB III Randomized Controlled Trial [RCT] [ABSORB-III]; NCT01751906; A Clinical Evaluation of Absorb Bioresorbable Vascular Scaffold [Absorb BVS] System in Chinese Population-ABSORB CHINA Randomized Controlled Trial [RCT] [ABSORB CHINA]; NCT01923740; ABSORB EXTEND Clinical Investigation [ABSORB EXTEND]; NCT01023789; AVJ-301 Clinical Trial: A Clinical Evaluation of AVJ-301 [Absorb BVS] in Japanese Population [ABSORB JAPAN]; NCT01844284).

Underutilization of Coronary Artery Disease Testing Among Patients Hospitalized With New-Onset Heart Failure

BACKGROUNDnAlthough ischemic coronary artery disease (CAD) is the most common etiology of heart failure (HF), the extent to which patients with new-onset HF actually undergo an ischemic work-up and/or revascularization is not well defined.nnnOBJECTIVESnThis study sought to analyze the patterns of testing for ischemic CAD and revascularization in patients with new-onset HF.nnnMETHODSnThis was a retrospective cohort study using Truven Health MarketScan Commercial and Medicare databases from 2010 to 2013. The occurrence of noninvasive and invasive ischemic CAD testing and revascularization procedures were examined among patients with new inpatient HF diagnoses during the index hospitalization and within 90 days of admission.nnnRESULTSnAmong 67,161 patients identified with new-onset HF during an inpatient hospitalization, only 17.5% underwent testing for ischemic CAD during the index hospitalization, increasing to 27.4% at 90 days. Among patients with new-onset HF, only 2.1% underwent revascularization during the index hospitalization for HF; by 90 days, the revascularization rate had increased to 4.3%. Of the tests performed for ischemic CAD, stress testing (nuclear stress testing or stress echocardiography) was performed in 7.9% of new-onset HF patients during the index hospitalization (14.6% within 90 days), whereas coronary angiography was performed in 11.1% of patients during the index hospitalization (16.5% within 90 days). In adjusted analyses, HF patients carrying a baseline diagnosis of CAD had greater odds of noninvasive ischemic testing (odds ratio: 1.25; 95% confidence interval: 1.17 to 1.33; pxa0< 0.0001), as well as invasive ischemic testing (odds ratio: 1.93; 95% confidence interval: 1.83 to 2.05; pxa0< 0.0001), at the index hospitalization than those without baseline CAD.nnnCONCLUSIONSnThe majority of patients hospitalized for new-onset HF did not receive testing for ischemic CAD either during hospitalization or within 90 days, which suggests significant underutilization of ischemic CAD assessment in new-onset HF patients.