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Biomedical subjects

Neil J Weissman

Publications and source records attributed to Neil J Weissman.

At least 19 recordsLinked to original sources

Two-year follow-up of the quantitative angiographic and volumetric intravascular ultrasound analysis after nonpolymeric paclitaxel-eluting stent implantation: late "catch-up" phenomenon from ASPECT Study.

OBJECTIVES: This study used serial angiographic and intravascular ultrasound (IVUS) analysis to evaluate the long-term efficacy of a nonpolymeric, paclitaxel-eluting stent coating on intimal hyperplasia (IH) 2 years after implantation. BACKGROUND: Long-term efficacy of patients treated with nonpolymeric paclitaxel-eluting stents beyond 1 year has not been well determined. METHODS: Patients were randomized to placebo or 1 of 2 doses of paclitaxel (low dose, 1.28 microg/mm2; high dose, 3.10 microg/mm2). Complete after-procedure, 6-month, and 2-year angiographic and IVUS data were available in 53 patients (17, 17, and 19 patients, respectively). RESULTS: Baseline characteristics were similar among the 3 groups. Although 6-month minimal luminal diameter (MLD) was significantly smaller in placebo compared with paclitaxel-eluting stent patients (1.9 +/- 0.6 mm in placebo, 2.5 +/- 0.6 mm in low-dose, and 2.6 +/- 0.5 mm in high-dose patients, p = 0.004), the MLDs at 2 years were similar (2.3 +/- 0.6 mm, 2.3 +/- 0.7 mm, and 2.0 +/- 0.8 mm, respectively, p = 0.4). Despite a stepwise reduction in IH accumulation at 6 months (23 +/- 18 mm3 in placebo, 14 +/- 11 mm3 in low-dose, and 10 +/- 12 mm3 in high-dose, p = 0.017), the increase of IH volume from 6 months to 2 years was significantly greater in the high-dose patients (13 +/- 14 mm3 in high-dose vs. 4 +/- 7 mm3 in low-dose patients, p = 0.074; and vs. 1 +/- 13 mm3 in placebo, p = 0.019). Late target lesion revascularization (beyond 1 year) was performed in 2 high-dose patients. CONCLUSIONS: Despite the suppression of IH after non-polymeric paclitaxel-eluting stents compared with bare-metal stents at 6 months, a "late catch-up" IH growth was found in the high-dose patients at 2-year follow-up.

Coronary Angiography↗

Frequency and severity of plaque prolapse within Cypher and Taxus stents as determined by sequential intravascular ultrasound analysis.

We used intravascular ultrasound to evaluate the incidence, characteristics, and clinical sequel of plaque prolapse within drug-eluting stents. The influence of stent design on plaque prolapse has not been studied. Drug-eluting stents were serially expanded, first at 14 atm and then at 20 atm, with intravascular ultrasound imaging after each inflation. The stent, lumen, and maximum plaque prolapse areas were measured. The residual lumen area and percentage of plaque prolapse burden (maximum plaque prolapse area/stent area) were calculated. Plaque prolapse was divided into grades 1 (<5%), 2 (5% to 10%), and 3 (10% to 20%). Eighty patients (83 lesions, 41 Cypher and 42 Taxus Express stents) were studied. The incidence of plaque prolapse was 41% (17 of 41 lesions) with the Cypher stents versus 24% (10 of 41 lesions) with the Taxus stents after 14 atm (p = 0.096) and 35% (14 of 40) in Cypher stents versus 17.8% (5 of 28) in Taxus stents after 20 atm (p = 0.17). However, the maximum plaque prolapse area was never >20% of the stent area. The frequency and amount of plaque prolapse neither increased nor decreased at higher (20 atm) inflation pressures. Lesions with prolapse were longer (p = 0.004), with a larger external elastic membrane area and greater plaque burden (each p <0.0001) and a larger remodeling index (p = 0.013). Conversely, nonprolapsed plaques had a higher incidence of superficial calcium (p = 0.001). Creatinine kinase-MB elevation was higher with plaque prolapse, and the magnitude of creatinine kinase-MB elevation correlated with the extent of plaque prolapse (r = 0.664, p = 0.002). Multiple logistic regression analysis indicated that a longer lesion length (p = 0.012), and smaller minimal luminal area (p = 0.031) had higher risks of plaque prolapse. In conclusion, plaque prolapse was frequently observed in Cypher and Taxus stents. However, sequential intravascular ultrasound imaging showed that the frequency and amount of plaque prolapse were neither increased nor decreased by additional higher pressure inflations.

Aged↗

Casq2 deletion causes sarcoplasmic reticulum volume increase, premature Ca2+ release, and catecholaminergic polymorphic ventricular tachycardia.

Cardiac calsequestrin (Casq2) is thought to be the key sarcoplasmic reticulum (SR) Ca2+ storage protein essential for SR Ca2+ release in mammalian heart. Human CASQ2 mutations are associated with catecholaminergic ventricular tachycardia. However, homozygous mutation carriers presumably lacking functional Casq2 display surprisingly normal cardiac contractility. Here we show that Casq2-null mice are viable and display normal SR Ca2+ release and contractile function under basal conditions. The mice exhibited striking increases in SR volume and near absence of the Casq2-binding proteins triadin-1 and junctin; upregulation of other Ca2+ -binding proteins was not apparent. Exposure to catecholamines in Casq2-null myocytes caused increased diastolic SR Ca2+ leak, resulting in premature spontaneous SR Ca2+ releases and triggered beats. In vivo, Casq2-null mice phenocopied the human arrhythmias. Thus, while the unique molecular and anatomic adaptive response to Casq2 deletion maintains functional SR Ca2+ storage, lack of Casq2 also causes increased diastolic SR Ca2+ leak, rendering Casq2-null mice susceptible to catecholaminergic ventricular arrhythmias.

Alleles↗

Intravascular ultrasound in the drug-eluting stent era.

Intravascular ultrasound (IVUS) has become an indispensable part of all drug-eluting stent (DES) studies; findings must be put into context with the IVUS findings in bare metal stents. Unfortunately, there is not yet a complete picture of either the Cypher (Cordis, Miami, Florida) or the Taxus (Boston Scientific, Maple Grove, Minnesota) stent (the two U.S. Food and Drug Administration-approved devices). Intimal hyperplasia volume in DES is reduced to <15% of stent volume, but stent underexpansion continues to be a consistent finding in DES failures (restenosis and thrombosis). The utility of IVUS to assure adequate stent expansion may be more important whenever there are clinical risk factors for DES failure.

Cardiology↗

Negative remodeling and calcified plaque in octogenarians with acute myocardial infarction: an intravascular ultrasound analysis.

OBJECTIVES: The goal of this study was to use intravascular ultrasound (IVUS) to compare octogenarians versus patients <65 years of age with regard to culprit lesion morphology in acute myocardial infarction (MI). BACKGROUND: Although octogenarians represent the fastest-growing segment of our population and have a higher risk profile, they are underrepresented in therapeutic trials. METHODS: Between 2002 and 2005, 42 octogenarians and 52 patients <65 years of age underwent pre-intervention IVUS within 2 days from onset of an MI. Qualitative and quantitative measurements were performed at the lesion site and at the proximal and distal references. Positive remodeling was defined as a remodeling index (lesion/mean reference arterial area) > or =1. RESULTS: Elderly patients mostly (71%) presented with non-ST-segment elevation myocardial infarction (NSTEMI), whereas patients <65 years of age presented almost equally with ST-segment elevation myocardial infarction (STEMI) and NSTEMI (56% vs. 44%). The frequency of rupture/dissection was greater in the <65-year-old group (32% vs. 9%, p = 0.009), and culprit lesions contained more thrombus in this group (14% vs. 2%, p = 0.04). Conversely, in octogenarians, lesions were predominantly calcified (57% vs. 10%, p < 0.001) and longer (20.9 +/- 7.8 mm vs. 16.6 +/- 6.1 mm, p = 0.004) with less positive remodeling (19% vs. 56%, p < 0.001). On multivariant logistic regression analysis, age was the only independent predictor of calcified plaque (p = 0.02) and remodeling (p = 0.005). CONCLUSIONS: Negative remodeling and calcified plaque with rare plaque ruptured were common in elderly people with acute MI. These findings may contribute to the difference in clinical presentation and may suggest a different pathophysiologic mechanism of MI in octogenarians.

Age Factors↗

Plaque characterization with optical coherence tomography.

The identification of unstable plaque is central in risk-stratifying patients for acute coronary events. Optical coherence tomography (OCT) is a recently introduced imaging modality that has shown considerable promise for the identification of high-risk plaques. Advantages of OCT include its high resolution (4 to 20 microm), high data acquisition rate, small and inexpensive guidewires/catheters, and ability to be combined with adjuvant optical techniques. This article summarizes the current state of intravascular OCT imaging, focusing on potential markers of instability and current limitations.

Animals↗

An intravascular ultrasound analysis of the mechanisms of restenosis comparing drug-eluting stents with brachytherapy.

There are treatment failures after de novo drug-eluting stent (DES) implantation and after treatment with DESs or vascular brachytherapy (VBT) of in-stent restenosis (ISR) lesions. We studied 38 patients who presented with DES failure (26 patients after de novo DES implantation and 12 patients after DES treatment of ISR) and 30 patients who presented with VBT failure (all after treatment of ISR). Standard clinical data were collected and volumetric intravascular ultrasound was measured. Patients who presented with DES failures were 58.8 +/- 9.6 years of age and those who presented with VBT failures were 59.8 +/- 8.7 years of age; 60.5% of DES and 58.6% of VBT failures were in men; 31.5% of DES failures and 46.6% of VBT failures occurred in diabetic patients; and times to presentation were 210 +/- 101 days in DES failures and 510 +/- 527 days in VBT failures (p = 0.001). Minimal stent area was significantly larger in VBT than in the 2 DES failure groups (de novo DES implantation and DES treatment of ISR, p <0.0001); this was associated with more neointimal hyperplasia in VBT failures (p <0.0001). After it was normalized to stent length, intimal hyperplasia was diffusely distributed in VBT failures; conversely, DES failures were associated with less intimal hyperplasia and the intimal hyperplasia was mostly focal, with greater accumulation in the proximal and mid segments. In conclusion, VBT failures were caused by significant, recurrent, and diffuse intimal hyperplasia in the setting of adequate stent expansion, whereas DES failures were caused by only modest, but focal, intimal hyperplasia in the setting of DES underexpansion.

Brachytherapy↗

New imaging techniques for diagnosing coronary artery disease.

New tomographic cardiovascular imaging tests, such as intravascular ultrasonography (IVUS), coronary computed tomography (CT) angiography and magnetic resonance imaging (MRI), can be used to assess atherosclerotic plaques for the characterization and early staging of coronary artery disease (CAD). Although IVUS images have very high resolution capable of revealing very early preclinical CAD, it is an invasive technique used clinically only in conjunction with a coronary intervention. Multiple-slice coronary CT angiography, which is noninvasive, shows promise as a diagnostic method for CAD. New 64-slice cardiac CT technology has high accuracy for the detection of lesions obstructing more than 50% of the lumen, with sensitivity, specificity, and positive and negative predictive values all better than 90% in patients without known CAD. Cardiac MRI is also improving accuracy in coronary plaque detection and offers a better opportunity for plaque characterization. With further advances in tomographic imaging of coronary atheromas, the goal will be to detect plaques earlier in the development of CAD and to characterize the plaques most likely to generate a clinical event.

Coronary Angiography↗

Safety and feasibility of transendocardial autologous bone marrow cell transplantation in patients with advanced heart disease.

The present report contains the final results of a Phase I study that evaluated the feasibility, safety, and potential efficacy of intramyocardial injection of autologous bone marrow (BM) in "no-option" patients with refractory angina and myocardial ischemia. Twenty-seven patients underwent electromechanic mapping-guided transendomyocardial injections (n = 12, 0.2 ml each) of unfractionated autologous BM cells directed to ischemic, noninfarcted myocardial territory. Patients were injected with 28 +/- 27 x 10(6)/ml nucleated cells containing 2.2 +/- 1.4% CD34+ cells. The autologous BM injection procedure was successful in all patients and was associated with no adverse events. At 3 months, the Canadian Cardiovascular Society angina score (3.2 +/- 0.5 vs 2.0 +/- 0.91, p = 0.001) and treadmill exercise duration (418 +/- 136 vs 489 +/- 142 seconds, p = 0.017) had improved significantly. The stress-induced ischemia score within the injected territories (118 segments) had also improved (2.2 +/- 0.8 vs 1.7 +/- 1.1, p < 0.001). At 1 year, the clinical improvement was sustained, although 5 patients had undergone revascularization procedures. The number of total injected nucleated cells (CD45+), progenitor cells (CD34+), and the magnitude of secreted vascular endothelial growth factor and macrophage chemoattractant protein-1 by cultured BM cells failed to predict the clinical response. In conclusion, the 3- and 12-month study results have indicated the safety of catheter-based transendocardial delivery of autologous BM cells in patients with advanced symptomatic ischemic heart disease and may suggest sustained potential efficacy. The cellular and humeral characteristics of autologous BM cells did not predict the clinical response, underscoring the advisability of additional mechanistic exploration.

Angina, Unstable↗

Comparison of ruptured plaques in native coronary arteries and in saphenous vein grafts: an intravascular ultrasound study.

Intravascular ultrasound (IVUS) has been used to describe ruptured plaques in saphenous vein grafts (SVGs) and native coronary arteries. We compared clinical, angiographic, and IVUS features of ruptured atherosclerotic plaques in SVGs and native coronary arteries. We identified 95 plaque ruptures in 76 SVGs in 73 patients. These lesions and patients were matched with 95 lesions and patients from a database of 468 native artery ruptures. The matching criterion was IVUS mean reference lumen area. Patients with ruptured SVG plaques were older (68.4 +/- 10.1 vs 65.0 +/- 10.6 years, p = 0.021), more often had hypercholesterolemia (92% vs 74%, p = 0.015) and hypertension (78% vs 62%, p = 0.059), and more often had a history of a remote myocardial infarction (57% vs 32%, p = 0.002). In contrast, anginal symptoms were similar in the 2 groups (70% to 75% of each group had an acute coronary syndrome). Most (90% to 95%) ruptured plaques in each group were classified as angiographically complex. However, ruptured SVG lesions more often had an angiographically visible intimal flap (71% vs 38%, p <0.001). More than 70% of lesions in the 2 groups had positive arterial remodeling by IVUS, but there was a tendency for a higher remodeling index in ruptured plaque SVG lesions (1.18 +/- 0.30 vs 1.11 +/- 0.20, p = 0.085). The site of the initial tear occurred mainly (in approximately 70%) at the plaque shoulders in the 2 groups. In conclusion, although patients with SVG plaque ruptures are older and have more co-morbidities, the clinical presentation and angiographic and IVUS features are remarkably similar to those of native artery plaque ruptures.

Aged↗

Percutaneous coronary intervention with drug-eluting stents in octogenarians: characteristics, clinical presentation, and outcomes.

OBJECTIVES: We aimed to compare clinical outcomes of octogenarians > or =80 years of age after coronary drug-eluting stent (DES) implantation. BACKGROUND: Although octogenarians constitute a fast-growing portion of cardiovascular patients, they are not adequately represented in current clinical revascularization trials. METHODS: We analyzed the data of 3,166 consecutive patients who underwent percutaneous coronary intervention (PCI) and DES implantation since March 2003. Periprocedural events, 1- and 6-month clinical outcomes were compared between octogenarians (n = 339) and patients <80 years of age (n = 2,827). RESULTS: Baseline characteristics revealed a higher prevalence of females (P < 0.001), Caucasians (P = 0.004), chronic renal failure (P < 0.001), heart failure (P < 0.001), number of diseased vessels (P = 0.009), and lower ejection fraction (P = 0.03) in octogenarians. Patients <80 years showed more positive family history (P < 0.001), hyperlipidemia (P = 0.006), smoking (P < 0.001), and obesity (P < 0.001). Clinical presentation and procedural success were similar in both groups as were death, myocardial infarction (MI), and repeat revascularization in-hospital. At 6 months, restenosis rates were low and comparable. In the subgroup of octogenarians who presented with acute coronary syndrome, mortality (15% vs. 3%, P < 0.001) and Q-wave MI occurred more often. Multivariate analysis revealed age >80 (P = 0.008), cardiogenic shock (P < 0.001), Q-wave MI at presentation (P = 0.003), and length of hospital stay (P = 0.003) to be independent predictors of mortality. CONCLUSIONS: PCI with DES in octogenarians results in a similar reduction of restenosis rates when compared to patients <80 years. Yet in octogenarians who presented with acute coronary syndrome, incidence of mortality and Q-wave MI at 6 months was higher as compared to younger patients.

Aged↗

Pivotal, randomized U.S. study of the Symbiottrade mark covered stent system in patients with saphenous vein graft disease: eight-month angiographic and clinical results from the Symbiot III trial.

OBJECTIVES: The purpose of this study was to evaluate the clinical and angiographic outcomes of the Symbiot ePTFE covered stent versus bare metal stents (BMS) for the treatment of saphenous vein graft (SVG) disease. BACKGROUND: The Symbiot stent was developed to reduce periprocedural complications, by potentially preventing distal embolization, and to serve as a possible barrier to cell migration, thus reducing restenosis. METHODS: Symbiot III is a prospective, randomized trial of 400 patients at 45 US sites, with 201 patients in the Symbiot group and 199 in the BMS group. Randomization was stratified based on the intended use of embolic protection devices and glycoprotein IIb/IIIa inhibitors. The primary endpoint was percent diameter stenosis (%DS) as measured by quantitative coronary angiography at 8 months. Secondary endpoints included MACE (cardiac death, MI, TVR). RESULTS: The groups were well matched for all baseline clinical and lesion characteristics. At 8 months, %DS was comparable between groups (30.9% Symbiot, 31.9% BMS, P = 0.80). Although the rates of binary restenosis in the stented segment were similar (29.1% Symbiot, 21.9% BMS, P = 0.17), more patients in the Symbiot group had binary restenosis at the proximal edge (9.0% Symbiot, 1.8% BMS, P = 0.0211). There was no difference in the incidence of MACE between groups (30.6% Symbiot, 26.6% BMS, P = 0.43). CONCLUSIONS: This study failed to show an advantage for the Symbiot stent in the treatment of degenerated SVGs. This PTFE covered stent does not appear to act as a barrier to prevent restenosis.

Adult↗

Intravascular ultrasound assessment of the spatial distribution of ruptured coronary plaques in the left anterior descending coronary artery.

BACKGROUND: Plaque rupture is a substrate for thrombosis, occlusion, and myocardial infarction. The left anterior descending coronary artery (LAD) subtends the largest amount of myocardium; therefore, the location of LAD plaque rupture is of particular importance in detecting vulnerable plaques. The aim of our study was to assess the location of ruptured atherosclerotic plaques in the LAD. METHODS: Using intravascular ultrasound, we detected 160 ruptured LAD plaques. Of these, accurate intravascular ultrasound distance measurements (with consistent automatic transducer pullback [0.5 mm/s] to the LAD ostium) could be determined in 112 ruptured plaques. RESULTS: There were 104 patients (91 men, age 63.8 +/- 11.7 years). The total length of the LAD that was imaged measured 48.8 +/- 24.8 mm. The distance from the LAD origin to the maximal plaque cavity was 16.2 +/- 10.3 mm; the maximal plaque cavity was localized to the first 20 mm of the LAD in 71% and the first 30 mm in 88%. Only 2 ruptured plaques were found beyond 40 mm from the LAD ostium. CONCLUSIONS: The majority of LAD ruptured plaques are located within the proximal 30 mm of the artery. This area of the LAD should be targeted for vulnerable (rupture-prone) plaque detection and prevention.

Aged↗

The impact of cardiovascular risk factors on subclinical left main coronary artery disease: an intravascular ultrasound study.

BACKGROUND: The impact of cardiovascular risk factors on subclinical but measurable left main coronary artery (LMCA) atherosclerosis is not well known. METHODS: We analyzed 150 consecutive patients with first-time coronary artery disease presentation undergoing intervention of a left anterior descending coronary artery or left circumflex lesion with motorized intravascular ultrasound transducer pullback that included a nonstenotic LMCA. Framingham, PROCAM, and European SCORE risk assessments were determined in 107 patients <65 years of age (because the Framingham, PROCAM, and European SCORE studies excluded patients >65 years old). Intravascular ultrasound measurements were compared in patients with <10% vs 10% to 20% risk of events. RESULTS: Plaque volumes were greater in patients with higher risk scores: P = .007 in patients with 10% to 20% PROCAM risk, P = .063 in patients with 10% to 20% Framingham risk, and P = .059 in patients with 10% to 20% SCORE risk (P = .059). The mean arc of LMCA calcium (12 degrees +/- 25 degrees overall) correlated with plaque volume (51 +/- 28 mm3, r = 0.30, P = .0001) and with the number of coronary risk factors (P = .048) and ranged from 0.28 degrees +/- 0.74 degrees in patients with 0 to 1 risk factors to 9.95 degrees +/- 21.55 degrees in patients with 2 to 4 risk factors to 19.38 degrees +/- 32.51 degrees in patients with 5 to 7 risk factors. Regression analysis showed obesity and age were the most important factors contributing to LMCA calcium. CONCLUSION: Intravascular ultrasound measurable atherosclerosis in nonstenotic LMCA correlates with conventional primary coronary risk scores. Left main coronary artery calcium correlates both with LMCA plaque volume and risk factors. Thus, subclinical LMCA atherosclerosis may be a marker for events that are predicted by commonly used primary risk-assessment algorithms.

Aging↗

Real-time 3-dimensional echocardiography evaluation of intracardiac masses.

UNLABELLED: The size of an intracardiac mass (vegetation, tumor, or thrombus) is an important predictor for embolic events and for response to treatment. Maximum diameter measurements from two-dimensional (2D) echocardiography are routinely used to determine mass size. However, most masses are irregularly shaped, making it difficult to accurately image or select the largest diameter. The selection of a diameter that is not truly the largest may lead to underestimation of the true size of the mass and a misrepresentation of the patients' prognosis. Three-dimensional (3D) echocardiography images the entire volume of a mass allowing for accurate measurements in multiple planes. We tested the hypothesis that measurements of the maximum diameter of a mass by 3D echocardiography are larger than those obtained by 2D echocardiography. METHODS: Patients with findings of an intracardiac mass by 2D transthoracic (TTE) or transesophageal (TEE) echocardiogram were imaged using real-time three-dimensional echocardiography (RT3DE) within 24 hours. The complete mass was acquired on RT3DE. Maximum mass diameter was measured on 2D and RT3DE. Comparison of measurements between RT3DE and 2D was performed using correlation coefficients and Bland-Altman analyses. RESULTS: In 19 masses evaluated in 17 patients, there was a strong correlation between 2D TTE and RT3DE maximum diameter measurements (R2 = 0.88, P < 0.01) but correlation was fair for 2D TEE (R2 = 0.48, P = 0.02). In addition, 2D maximum diameter also correlated with 3D volumes (R2 = 0.72, P < 0.01 for TTE and R2 = 0.56, P < 0.01 for TEE). However, there was a consistent underestimation of maximum diameter measured by 2D (TTE and TEE) regardless of the size, location, and etiology of the mass. 2D TTE underestimates cardiac mass size by 24.6% (P < 0.001) compared to RT3DE and 2D TEE underestimated size by 19.8% (P = 0.01). CONCLUSION: These findings suggest that RT3DE may be the technique of choice for the noninvasive evaluation of intracardiac mass size.

Coronary Thrombosis↗

Aortic stenosis and the failing heart.

The combination of aortic stenosis and left-ventricular dysfunction is a challenging situation for the physician. Diagnosis of this condition requires a detailed evaluation to understand the etiology and reversibility of the ventricular dysfunction and to accurately determine the real severity of the stenosis. Whether the aortic stenosis the cause of the left ventricular failure or is an independent disease has significant diagnostic, prognostic and therapeutic implications. Dobutamine echocardiography provides critical information to determine the real severity and the left ventricle's potential to recover (contractile reserve). Attempts to delay the progression of the aortic stenosis with medical treatment have been limited, and valve replacement remains the hallmark of ultimate treatment. If surgery is inadvertently delayed, left ventricular systolic dysfunction will result in clinically evident congestive heart failure and this situation carries a very high short-term mortality. Aortic valve replacement in this setting improves the outcome, but perioperative mortality is high, and particularly when coronary revascularization is also needed, there is no ventricular contractile reserve and transvalvular gradients are low. Adequate timing of surgery is extremely important and increasingly more difficult. Management decisions should be tailored by the results of dobutamine echocardiography and made on a case-by-case basis.

Animals↗