Clinical, angiographic and procedural correlates of quantitative coronary dimensions after directional coronary atherectomy

AbstractTo define the clinical, angiographic and procedural correlates of quantitative coronary dimensions after directional coronary atherectomy, 400 lesions in 378 patients were analyzed with use of qualitative morphologic and quantitative angiographic methods. Successful atherectomy, defined by a <75% residual area stenosis, tissue retrieval and the absence of in-hospital ischemic complications, was performed in 351 lesions (87.7%). After atherectomy, minimal cross-sectional area increased from 1.2 ± 1.1 to 6.6 ± 4.4 mm2(p < 0.001) and percent area stenosis was reduced from 87 ± 10% to 31 ± 42% (p < 0.001).By univariate analysis, device size (p < 0.001) and left circumflex artery lesion location (p = 0.004) were associated with a larger final minimal cross-sectional area. Conversely, restenotic lesion (p = 0.002), lesion length ≥ 10 mm (p = 0.018) and lesion calcification (p = 0.035) were quantitatively associated with a smaller final minimum cross-sectional area. With use of stepwise multivariate analysis to control for the reference area, atherectomy device size (p = 0.003) and left circumflex lesion location (p = 0.007) were independently associated with a larger final minimal cross-sectional area, whereas restenotic lesion (p = 0.010), diffuse proximal disease (p = 0.033), lesion length ≥ 10 mm (p = 0.026) and lesion calcification (p = 0.081) were significantly correlated with a smaller final minimal cross-sectional area. The number of specimens excised, the number of atherectomy passes and atherectomy balloon inflation pressure did not correlate with the final minimal cross-sectional area.Thus, directional atherectomy results in marked improvement of coronary lumen dimensions, at least in part correlated with the presence of certain clinical, angiographic and procedural factors at the time of atherectomy

CRT-700.1 Multi-Center Compassionate use Early Feasibility Evaluation of J-Valve Transcatheter Treatment for Severe Aortic Valve Regurgitation: Preliminary Results

Background: Although transcatheter aortic valve replacement (TAVR) is accepted therapy for treatment of symptomatic severe aortic valve stenosis (AS), current devices are associated with increased procedural complications and sub-optimal outcomes when used to treat of aortic valve regurgitation (AR). Severe AR is the indication for 20-30% of surgical aortic valve replacements and is associated with increased morbidity and mortality. J-valve is a short frame, self-expanding TAVR device. (Figure) specifically designed for treatment of severe AR. Anchor rings facilitate commissural alignment and secure attachment to non-calcified native valves. Methods: From Sept 2019 through Oct 2022, patients with symptomatic severe AR who were not surgical candidates or excluded from the ALIGN-AR trial were enrolled into a compassionate use early feasibility study at 5 North American centers. All patients signed informed consent for protocol approved by respective institutional review boards. Results: Data from 13/28 patients (mean age 80 yrs; 38.5% male) with symptomatic (92.3% NYHA class III/IV; mean LVEF 48% [range 23-64%]) severe (92% grade III/IV) AR, atrial fibrillation (53.8%), and pacemaker/ICD (15.4%), had J-valve TAVR (15.4% alternative access). There were no deaths to 30 days and post-procedural AR grade was none/trivial in all patients. In follow-up (mean 333 days) there are 0 cardiac deaths (total mortality 30.7%; 3 malignancies, 1 sepsis). Serial echocardiograms demonstrate AR grade none/mild in 89%, and 100% at 30 days and 1 year respectively). Conclusion: Despite high risk profile, preliminary analysis of this multi-center compassionate use study suggests that J-valve is safe with durable effectiveness for the treatment of symptomatic severe AR. Full data set on all patients will be presented

Mechanism of benefit of combination thrombolytic therapy for acute myocardial infarction: A quantitative angiographic and hematologic study

AbstractObjectives. The goal of this study was to lend insight into the mechanisms responsible for the beneficial effects of combination thrombolytic therapy.Background. Combination thrombolytic therapy for acute myocardial infarction bas been associated with less reocclusion and fewer in-hospital clinical events than has monotherapy.Methods. Infarct-related quantitative coronary dimensions and hemostatic protein levels were evaluated in 287 patients with acute myocardial infarction during the early (90-min) and convalescent (7-day) phases after administration of recombinant tissue-type plasminogen activator (rt-PA), urokinase or combination rt-PA and urokinase.Results. Minimal lumen diameter was similar in the 90-min and 7-day phases after treatment with rt-PA, urokinase and combination rt-PA and urokinase (0.72 ± 0.45 mm, 0.62 ± 0.53 mm and 0.75 ± 0.58 mm, respectively, at 90 min, p = 0.16; and 1.05 ± 0.56 mm, 1.12 ± 0.72 mm and 0.94 ± 0.54 mm, respectively, at 7 days, p = 0.22). In-hospital clinical event and reocclusion rates were less frequent in patients receiving combination therapy than in those receiving monotherapy (25% vs. 38% and 32% for rt-PA and urokinase, respectively, p = 0.084; and 3% vs. 13% and 9% for rt-PA and urokinase, respectively, p = 0.03), but these events were unrelated to early or late coronary dimensions. Patients receiving combination therapy or urokinase monotherapy had significantly higher peak fibrin degradation products (1,307 ± 860 and 1,285 ± 898 μg/ml vs. 435 ± 717 μg/ml, respectively, p < 0.0001) and lower nadir fibrinogen levels (0.85 ± 1.00 and 0.75 ± 0.53 g/liter vs. 1.90 ± 0.86 g/liter, respectively, p < 0.0001) than did those receiving rt-PA monotherapy. Peak fibrinogen degradation products indirectly correlated (p = 0.004) and baseline (p = 0.026) and nadir (p = 0.089) fibrinogen levels directly correlated with reocclusion.Conclusions. Lower in-hospital clinical event and reocclusion rates observed with combination thrombolytic therapy may relate to systemic hematologic factors rather than to the residual lumen obstruction after thrombolysis

Coronary bypass surgery improves global and regional left ventricular function following thrombolytic therapy for acute myocardial infarction

Coronary bypass surgery was performed prior to hospital discharge in 303 (22%) of 1387 consecutive patients enrolled in the TAMI 1 to 3 and 5 trials of intravenous thrombolytic therapy for acute myocardial infarction. Bypass surgery was of emergency nature (24 hours) in 267 (19.3%) patients. The indications for bypass surgery included falled angioplasty (12%); left main or equivalent coronary disease (9%); complex or multivessel coronary disease (62%); recurrent postinfarction angina (13%); and refractory pump dysfunction, mitral regurgitation, ventricular septal rupture or abnormal predischarge functional test (1% each). Although patients having bypass surgery were older (59.5 +/- 9.8 versus 56.0 +/- 10.2 years, (p p p = 0.048), had more prior infarctions (p p = 0.0002), and regional infarct zone (-2.7 +/- 0.94 versus -2.5 +/- 1.1 SD/chord, p = 0.02) and noninfarct zone function (-0.36 +/- 1.8 versus 0.43 +/- 1.6 SD/chord, p p = 0.036) and infarct zone regional function (0.71 +/- 1.1 versus 0.34 +/- 0.99 SD/chord, p = 0.001) when immediate (90 minutes following initiation of thrombolytic therapy) and predischarge (7 to 14 days after treatment) contrast left ventriculograms were compared than did patients who received only intravenous thrombolytic therapy with or without coronary angioplasty. These data suggest a beneficial influence of coronary bypass surgery on left ventricular function and possibly on the clinical outcome of patients initially treated with intravenous thrombolytic therapy for acute myocardial infarctionPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29209/1/0000263.pd

A prospective evaluation of the safety and efficacy of the TAXUS Element paclitaxel-eluting coronary stent system for the treatment of de novo coronary artery lesions: Design and statistical methods of the PERSEUS clinical program

<p>Abstract</p> <p>Background</p> <p>Paclitaxel-eluting stents decrease angiographic and clinical restenosis following percutaneous coronary intervention compared to bare metal stents. TAXUS Element is a third-generation paclitaxel-eluting stent which incorporates a novel, thinner-strut, platinum-enriched metal alloy platform. The stent is intended to have enhanced radiopacity and improved deliverability compared to other paclitaxel-eluting stents. The safety and efficacy of the TAXUS Element stent are being evaluated in the pivotal PERSEUS clinical trials.</p> <p>Methods/Design</p> <p>The PERSEUS trials include two parallel studies of the TAXUS Element stent in single, de novo coronary atherosclerotic lesions. The PERSEUS Workhorse study is a prospective, randomized (3:1), single-blind, non-inferiority trial in subjects with lesion length ≤28 mm and vessel diameter ≥2.75 mm to ≤4.0 mm which compares TAXUS Element to the TAXUS Express²paclitaxel-eluting stent system. The Workhorse study employs a novel Bayesian statistical approach that uses prior information to limit the number of study subjects exposed to the investigational device and thus provide a safer and more efficient analysis of the TAXUS Element stent. PERSEUS Small Vessel is a prospective, single-arm, superiority trial in subjects with lesion length ≤20 mm and vessel diameter ≥2.25 mm to <2.75 mm that compares TAXUS Element with a matched historical bare metal Express stent control.</p> <p>Discussion</p> <p>The TAXUS PERSEUS clinical trial program uses a novel statistical approach to evaluate whether design and metal alloy iterations in the TAXUS Element stent platform provide comparable safety and improved procedural performance compared to the previous generation Express stent. PERSEUS trial enrollment is complete and primary endpoint data are expected in 2010. PERSEUS Workhorse and Small Vessel are registered at <url>http://www.clinicaltrials.gov</url>, identification numbers NCT00484315 and NCT00489541.</p

Quantitative analysis of factors influencing late lumen loss and restenosis after directional coronary atherectomy

Although encouraging initial results have been demonstrated after directional atherectomy, the mechanisms and predictors of late lumen loss and restenosis after this procedure have not been evaluated. To examine these issues, clinical and angiographic follow-up were obtained in 262 (96%) and 212 (77%) of 274 patients undergoing successful directional coronary atherectomy. Symptom recurrence developed in 87 (33%) patients and angiographic restenosis was found in 93 (44%). Restenosis was highest in restenotic lesions in saphenous vein grafts (78% [95% confidence interval (CI): 56 to 100%]) and lowest in new-onset lesions in the left anterior descending (27% [95% CI: 15 to 39%]) and circumflex (14% [95% CI: 0 to 43%]) coronary arteries. Residual lumen diameter immediately after atherectomy was smaller in re-stenotic lesions (p = 0.002) and in lesions &gt;=10 mm in length (p = 0.02). Late lumen loss was associated with the minimal lumen diameter immediately after atherectomy (p =10 mm in length (p = 0.018), saphenous vein graft lesion location (p = 0.025) and male gender (p = 0.045) were independent predictors for restenosis. It is concluded that restenosis after directional atherectomy is related both to factors resulting in a suboptimal initial result and to factors contributing to excessive late lumen loss. These results may have implications for lesion selection in patients undergoing directional coronary atherectomy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30957/1/0000629.pd

Complete atrioventricular block complicating inferior wall acute myocardial infarction treated with reperfusion therapy

Previous studies report larger myocardial infants and increased in-hospital mortality rates in patients with inferior wall acute myocardial infarction (AMI) and complete atrioventricular block (AV), but the clinical implications of these complications in patients treated with reperfusion therapy have not been addressed. The clinical course of 373 patients--50 (13%) of whom developed complete AV block--admitted with inferior wall AMI and given thrombolytic therapy within 6 hours of symptom onset was studied. Acute patency rates of the infarct artery after thrombolytic therapy were similar in patients with or without AV block. Ventricular function measured at baseline and before discharge in patients with complete AV block showed a decrement in median ejection fraction (-3.5 vs -0.4%, P = 0.03) and in median regional wall motion (-0.14 vs +0.24 standard deviations/chord, P = 0.05). The reocclusion rate was higher in patients with complete AV block (29 vs 16%, P = 0.03). Patients with complete AV block had more episodes of ventricular fibrillation or tachycardia (36 vs 14%, p &lt; 0.001), sustained hypotension (36 vs 10%, p &lt; 0.001), pulmonary edema (12 vs 4%, P = 0.02) and a higher in-hospital mortality rate (20 vs 4%, p &lt; 0.001), although the mortality rate after hospital discharge was identical (2%) in the 2 groups. Multivariable logistic regression analysis revealed that complete AV block was a strong independent predictor of in-hospital mortality (p = 0.0006). Thus, despite initial successful reperfusion, patients with inferior wall AMI and complete AV block have higher rates of in-hospital complications and mortality.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29481/1/0000567.pd

Efficacy and safety of alirocumab in insulin-treated patients with type 1 or type 2 diabetes and high cardiovascular risk:Rationale and design of the ODYSSEY DM-INSULIN trial

Aims: The coadministration of alirocumab, a PCSK9 inhibitor for treatment of hypercholesterolaemia, and insulin in diabetes mellitus (DM) requires further study. Described here is the rationale behind a phase-IIIb study designed to characterize the efficacy and safety of alirocumab in insulin-treated patients with type 1 (T1) or type 2 (T2) DM with hypercholesterolaemia and high cardiovascular (CV) risk. Methods: ODYSSEY DM-INSULIN (NCT02585778) is a randomized, double-blind, placebo-controlled, multicentre study that planned to enrol around 400 T2 and up to 100 T1 insulin-treated DM patients. Participants had low-density lipoprotein cholesterol (LDL-C) levels at screening. ≥. 70. mg/dL (1.81. mmol/L) with stable maximum tolerated statin therapy or were statin-intolerant, and taking (or not) other lipid-lowering therapy; they also had established CV disease or at least one additional CV risk factor. Eligible patients were randomized 2:1 to 24. weeks of alirocumab 75. mg every 2. weeks (Q2W) or a placebo. Alirocumab-treated patients with LDL-C. ≥. 70. mg/dL at week 8 underwent a blinded dose increase to 150. mg Q2W at week 12. Primary endpoints were the difference between treatment arms in percentage change of calculated LDL-C from baseline to week 24, and alirocumab safety. Results: This is an ongoing clinical trial, with 76 T1 and 441 T2 DM patients enrolled; results are expected in mid-2017. Conclusion: The ODYSSEY DM-INSULIN study will provide information on the efficacy and safety of alirocumab in insulin-treated individuals with T1 or T2 DM who are at high CV risk and have hypercholesterolaemia not adequately controlled by the maximum tolerated statin therapy

Transcatheter or surgical aortic-valve replacement in intermediate-risk patients

BACKGROUND: Previous trials have shown that among high-risk patients with aortic stenosis, survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical aorticvalve replacement. We evaluated the two procedures in a randomized trial involving intermediate-risk patients. METHODS: We randomly assigned 2032 intermediate-risk patients with severe aortic stenosis, at 57 centers, to undergo either TAVR or surgical replacement. The primary end point was death from any cause or disabling stroke at 2 years. The primary hypothesis was that TAVR would not be inferior to surgical replacement. Before randomization, patients were entered into one of two cohorts on the basis of clinical and imaging findings; 76.3% of the patients were included in the transfemoral-access cohort and 23.7% in the transthoracic-access cohort. RESULTS: The rate of death from any cause or disabling stroke was similar in the TAVR group and the surgery group (P=0.001 for noninferiority). At 2 years, the Kaplan–Meier event rates were 19.3% in the TAVR group and 21.1% in the surgery group (hazard ratio in the TAVR group, 0.89; 95% confidence interval [CI], 0.73 to 1.09; P=0.25). In the transfemoralaccess cohort, TAVR resulted in a lower rate of death or disabling stroke than surgery (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P=0.05), whereas in the transthoracic-access cohort, outcomes were similar in the two groups. TAVR resulted in larger aortic-valve areas than did surgery and also resulted in lower rates of acute kidney injury, severe bleeding, and new-onset atrial fibrillation; surgery resulted in fewer major vascular complications and less paravalvular aortic regurgitation. CONCLUSIONS: In intermediate-risk patients, TAVR was similar to surgical aortic-valve replacement with respect to the primary end point of death or disabling stroke. (Funded by Edwards Lifesciences; PARTNER 2 ClinicalTrials.gov number, NCT01314313