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Chronic wounds are a major health problem that cause the medical infrastructure billions of dollars every year. Chronic wounds are often difficult to heal and cause significant discomfort. Although wound specialists have numerous therapeutic modalities at their disposal, tools that could 3D-map wound bed physiology and guide therapy do not exist. Visual cues are the current standard but are limited to surface assessment; clinicians rely on experience to predict response to therapy. Photoacoustic (PA) ultrasound (US) is a non-invasive, hybrid imaging modality that can solve these major limitations. PA relies on the contrast generated by hemoglobin in blood which allows it to map local angiogenesis, tissue perfusion and oxygen saturation—all critical parameters for wound healing. This work evaluates the use of PA-US to monitor angiogenesis and stratify patients responding vs. not-responding to therapy. We imaged 19 patients with 22 wounds once a week for at least three weeks. Our findings suggest that PA imaging directly visualizes angiogenesis. Patients responding to therapy showed clear signs of angiogenesis and an increased rate of PA increase (p = 0.002). These responders had a significant and negative correlation between PA intensity and wound size. Hypertension was correlated to impaired angiogenesis in non-responsive patients. The rate of PA increase and hence the rate of angiogenesis was able to predict healing times within 30 days from the start of monitoring (power = 88%, alpha = 0.05) This early response detection system could help inform management and treatment strategies while improving outcomes and reducing costs.

Facemasks in congregate settings prevent the transmission of SARS-CoV-2 and help control the ongoing COVID-19 global pandemic because face coverings can arrest transmission of respiratory droplets. While many groups have studied face coverings as personal protective equipment, these respiratory droplets can also serve as a diagnostic fluid to report on health state; surprisingly, studies of face coverings from this perspective are quite limited. Here, we determined the concentration and distribution of aerosolized saliva (via α-amylase levels) captured on various face coverings. Our results showed that α-amylase accumulated on face coverings in a time-dependent way albeit at different levels, e.g., neck gaiters and surgical masks captured about 3-fold more α-amylase than cloth masks and N95 respirators. In addition, the saliva aerosols were primarily detected on the inner layer of multilayered face coverings. We also found that the distribution of salivary droplets on the mask correlated with the morphologies of face coverings as well as their coherence to the face curvature. These findings motivated us to extend this work and build multifunctional sensing strips capable of detecting biomarkers in situ to create “smart” masks. The work highlights that face coverings are promising platforms for biofluid collection and colorimetric biosensing, which bode well for developing surveillance tools for airborne diseases.

The transmission of SARS-CoV-2 coronavirus has led to the COVID-19 pandemic. Nucleic acid testing while specific has limitations for mass surveillance. One alternative is the main protease (M(pro)) due to its functional importance in mediating the viral life cycle. Here, we describe a combination of modular substrate and gold colloids to detect M(pro) via visual readout. The strategy involves zwitterionic peptide that carries opposite charges at the C-/N-terminus to exploit the specific recognition by M(pro). Autolytic cleavage releases positively-charged moiety that assembles the nanoparticles with rapid color changes (t

There is a need for surveillance of COVID-19 to identify individuals infected with SARS-CoV-2 coronavirus. Although specific, nucleic acid testing has limitations in terms of point-of-care testing. One potential alternative is the nonstructural protease (nsp5, also known as Mpro/3CLpro) implicated in SARS-CoV-2 viral replication but not incorporated into virions. Here, we report a divalent substrate with a novel design, (Cys)2–(AA)x–(Asp)3, to interface gold colloids in the specific presence of Mpro leading to a rapid and colorimetric readout. Citrate- and tris(2-carboxyethyl)phosphine (TCEP)-AuNPs were identified as the best reporter out of the 17 ligated nanoparticles. Furthermore, we empirically determined the effects of varying cysteine valence and biological media on the sensor specificity and sensitivity. The divalent peptide was specific to Mpro, that is, there was no response when tested with other proteins or enzymes. Furthermore, the Mpro detection limits in Tris buffer and exhaled breath matrices are 12.2 and 18.9 nM, respectively, which are comparable to other reported methods (i.e., at low nanomolar concentrations) yet with a rapid and visual readout. These results from our work would provide informative rationales to design a practical and noninvasive alternative for COVID-19 diagnostic testing—the presence of viral proteases in biofluids is validated.

Heparin is a common anticoagulant, but heparin overdose is a common intensive care unit (ICU) medication error due to the narrow therapeutic window of heparin. Conventional methods to monitoring heparin suffer from long turnaround time, the need for skilled personnel, and low frequency of sampling. To overcome these issues, we describe here a fiber optic photoacoustic (PA) sensor for real-time heparin monitoring. The proposed sensor was validated with in vitro testing and in a simulated in vivo model using the following samples: (1) phosphate-buffered saline (PBS), (2) spiked human plasma, (3) spiked whole human blood, and (4) clinical samples from patients treated with heparin. Samples were validated by comparing the PA signal to the activated partial thromboplastin time (aPTT) as well as the activated clotting time (ACT). Importantly, the proposed sensor has a short turnaround time (3min) and a limit of detection of 0.18 U/ml in whole human blood. The PA signal is linear with heparin dose and correlates with the aPTT value (Pearson's r=0.99). The PA signal from 32 clinical samples collected from eight patients linearly correlated with ACT values (Pearson's r=0.89, in vitro; Pearson's r=0.93, simulated in vivo). The PA signal was also validated against the cumulative heparin dose (Pearson's r=0.94, in vitro; Pearson's r=0.96, simulated in vivo). This approach could have applications in both in vitro and real-time in vivo heparin monitoring.

Chronic wounds can be difficult to heal and are often accompanied by pain and discomfort. Multiple skin substitutes or cellularized/tissue-based skin products have been used in an attempt to facilitate closure of complex wounds. Allografts from cadaveric sources have been a viable option in achieving such closure. However, early assessment of graft incorporation has been difficult clinically, often with delayed evidence of failure. Visual cues to assess graft integrity have been limited and remain largely superficial at the skin surface. Furthermore, currently used optical imaging techniques can penetrate only a few millimeters deep into tissue. Ultrasound (US) imaging offers a potential solution to address this limitation. This work evaluates the use of US to monitor wound healing and allograft integration. We used a commercially available dual-mode (US and photoacoustic) scanner operating only in US mode. We compared the reported wound size from the clinic with the size measured using US in 45 patients. Two patients from this cohort received an allogenic skin graft and underwent multiple US scans over a 110-d period. All data were processed by two independent analysts; one of them was blinded to the study. We measured change in US intensity and wound contraction as a function of time. Our results revealed a strong correlation (R2=0.81, p < 0.0001) between clinically and US-measured wound sizes. Wound contraction >91% was seen in both patients after skin grafting. An inverse relationship between wound size and US intensity (R2=0.77, p < 0 .0001) indicated that the echogenicity of the wound bed increases as healthy cells infiltrate the allograft matrix, regenerating and leading to healthy tissue and re-epithelization. This work indicates that US can be used to measure wound size and visualize tissue regeneration during the healing process.

SVG aneurysms are relatively rare clinical entities most often encountered discovered as an incidental finding in patients with prior CABG surgery. There is a substantial risk of complications including rupture and death, thus surgical or percutaneous management may be considered in particular in symptomatic patients. Here, three cases are presented highlighting various percutaneous management options and considerations, including covered stent placement, coil occlusion, and a combined approach with the use of a peripheral covered stent. Intervention within this patient population lacks large population long-term outcomes and as such should be performed carefully by experienced operators, often the guidance of a Heart Team based approach.

Objective The objective of this qualitative review is to summarize the pathophysiological and clinical data behind the clinical entity of left internal mammary artery (LIMA) side branch coronary steal as well as the potential diagnostic and therapeutic modalities available. Background The presence of persistent unligated LIMA side branches following coronary artery bypass grafting has previously been associated with stable angina and acute coronary syndromes. However, despite numerous attempts to objectively demonstrate a coronary steal phenomenon, the pathophysiology of LIMA side branch flow diversion remains elusive and the clinical utility of intervention is not well elucidated. Methods A review of literature and available data including case reports, case series, and investigational studies was performed. Results Therapeutic closure of LIMA side branches has been reported in at least 44 patients and in at least 31 publications since 1990 and is associated with an 87.5% rate of freedom from angina amongst technically successful initial interventions. In all patients with pre- and post- stress testing, intervention was associated with an improvement and/or resolution of previously observed reversible ischemia. Conclusions LIMA side branch coronary steal should remain an ongoing consideration in symptomatic patients with large unligated side branches on angiography, particularly when there is clear evidence of reversible ischemic on perfusion imaging.

Heparin is an indispensable drug in anticoagulation therapy but with a narrow therapeutic window, which dictates regular testing and dose adjustment. However, current monitoring tools have a long turnaround time or are operator intensive. In this work, we describe a cellulose-based photoacoustic sensor for heparin. The sensors have a turnaround time of 6 min for whole blood samples and 3 min for plasma samples regardless of heparin concentration. These sensors have a limit of detection of 0.28 U/ml heparin in human plasma and 0.29 U/ml in whole blood with a linear response (Pearson's r = 0.99) from 0 to 2 U/ml heparin in plasma and blood samples. The relative standard deviation was

Background Ticagrelor presents less thrombotic risk compared to clopidogrel in acute coronary syndromes. However, its role in dual antiplatelet therapy (DAPT)-naive patients with stable ischemic heart disease (SIHD) undergoing elective percutaneous intervention (PCI) remains unclear, including uncertainty in the method of conversion to clopidogrel for adequate coverage without increased bleeding risk. Objective Determine the safety and efficacy of ticagrelor loading and transitioning to clopidogrel in patients with SIHD undergoing elective PCI. Methods This is a retrospective cohort review of patients with SIHD who underwent elective PCI. The Switch Rx patients were treated with ticagrelor immediately before PCI, converted to clopidogrel 300 mg the day after, and discharged with clopidogrel 75 mg daily. Standard Rx patients, who received a clopidogrel load and received clopidogrel 75 mg daily after the procedure, were analyzed as a matched comparator cohort. The safety outcomes were any bleeding event at 24 hours and 30 days. The efficacy outcomes included major adverse cardiac events (MACE) at 24 hours and 30 days. Results Five Switch Rx patients (n = 54) experienced bleeding academic research consortium type I bleeding within 24 hours, with no subsequent bleeding observed out to 30 days. When comparing the Switch Rx patients (n = 39) to their matched Standard Rx cohort (n = 39), no MACEs occurred within 30 days and there were no significant differences in safety and efficacy outcomes. Conclusion In DAPT-naive patients undergoing elective PCI for SIHD, a strategy of in-lab ticagrelor transitioning to clopidogrel with a 300-mg load was not associated with increased bleeding or other adverse events.

Transcatheter aortic valve replacement (TAVR) is a minimally invasive cardiac surgical procedure that has revolutionized the treatment of aortic stenosis. This is the most common valvular heart condition in developed countries, affecting 3.4% of those ages 75 and above. Because there is no medical therapy that can arrest progression of the disease, valve replacement forms the cornerstone of therapy.Naval Medical Center San Diego and the VA San Diego Healthcare System have developed a unique collaborative TAVR program-a first in the Department of Defense-to offer this revolutionary procedure to their beneficiaries. Herein, we review development of the program and outcome for patients referred during the first 9 months.Development of the program was a multiyear process made successful because of administrative support, facility upgrades, and collaboration within the crossfacility and multispecialty heart valve team. In the first 9 months, 29 patients were referred for evaluation. Twenty-two (average age 80 years) underwent TAVR, whereas others were deemed nonoperable or were pending disposition at the time of this report. Patients who underwent TAVR had a predicted risk of procedural mortality from surgical aortic valve replacement of 7.7%, similar to other trials and registry studies. After mean follow-up of 5.6 months (range 30-355 days), zero deaths were recorded in the patients who underwent TAVR. Compared to other nonfederal local institutions, the program also realized a cost savings of approximately 17%, or nearly $10,000, per patient.In the first 9 months, results were positive and consistent with expectations from national and international registries. Our hope is that this program may serve as an example for other federal facilities looking to start their own combined programs to improve health care quality and patient experience while simultaneously achieving considerable cost containment within a constrained national health care budget.

Objectives The aim of this study was to examine the frequency, associations, and outcomes of native coronary artery versus bypass graft percutaneous coronary intervention (PCI) in patients with prior coronary artery bypass grafting (CABG) in the Veterans Affairs (VA) integrated health care system. Background Patients with prior CABG surgery often undergo PCI, but the association between PCI target vessel and short- and long-term outcomes has received limited study. Methods A national cohort of 11,118 veterans with prior CABG who underwent PCI between October 2005 and September 2013 at 67 VA hospitals was examined, and the outcomes of patients who underwent native coronary versus bypass graft PCI were compared. Logistic regression with generalized estimating equations was used to adjust for correlation between patients within hospitals. Cox regressions were modeled for each outcome to determine the variables with significant hazard ratios (HRs). Results During the study period, patients with prior CABG represented 18.5% of all patients undergoing PCI (11,118 of 60,171). The PCI target vessel was a native coronary artery in 73.4% and a bypass graft in 26.6%: 25.0% in a saphenous vein graft and 1.5% in an arterial graft. Compared with patients undergoing native coronary artery PCI, those undergoing bypass graft PCI had higher risk characteristics and more procedure-related complications. During a median follow-up period of 3.11 years, bypass graft PCI was associated with significantly higher mortality (adjusted HR: 1.30; 95% confidence interval: 1.18 to 1.42), myocardial infarction (adjusted HR: 1.61; 95% confidence interval: 1.43 to 1.82), and repeat revascularization (adjusted HR: 1.60; 95% confidence interval: 1.50 to 1.71). Conclusions In a national cohort of veterans, almost three-quarters of PCIs performed in patients with prior CABG involved native coronary artery lesions. Compared with native coronary PCI, bypass graft PCI was significantly associated with higher incidence of short- and long-term major adverse events, including more than double the rate of in-hospital mortality.

Background Pre-procedural anemia is associated with increased bleeding and mortality post-percutaneous coronary intervention (PCI). The effect of trans-radial PCI (TR-PCI) in improving outcomes compared to trans-femoral PCI (TF-PCI) in anemic patients is not known. Objective The aim of this study was to evaluate the association between arterial access site (radial versus femoral) and outcomes in anemic Veterans undergoing PCI. Methods Patients with baseline anemia, undergoing PCI at Veterans Affairs (VA) facilities between 2009 and 2015, were divided into two groups based on primary radial or femoral access. The association between anemia and access site with in-hospital and one-year adverse outcomes was evaluated using multivariable analysis. Results 7330 veterans were included in the analysis, with 1712 (23%) treated via radial access. Baseline anemia was independently associated with in-hospital major bleeding (OR 3.8, 95% CI 2.5–5.6 for moderate anemia, OR 18.6, 95% CI 11.6–29.7 for severe anemia), and in-hospital mortality (OR 3.2, 95% CI 1.8–5.8 for moderate anemia, OR 7.9, 95% CI 3.7–16.8 for severe anemia). Anemia was also associated with increased one-year MACE and mortality. PCI performed via radial access was not associated with different outcomes compared with femoral access in the presence of anemia. Comparable results were noted when analysis was restricted to only patients with acute coronary syndrome (ACS). Conclusions Moderate and severe anemia were strongly associated with increased in-hospital and one-year mortality in a large healthcare system, though there was no interaction between arterial access site for PCI and clinical outcomes among patients with moderate or severe anemia.

The prognosis of patients with HFrEF remains poor despite the use of current medical and device therapies. Preclinical studies of HFrEF using IC delivery of RT-100, a replication deficient, E1/E3-deleted human adenovirus 5 encoding human AC6 was associated with favorable effects on LV function and remodeling. A recent multicenter, double-blind, placebo-controlled, phase 2 study demonstrated the safety of IC delivery of RT-100 in HFrEF patients and potential efficacy at the higher doses. This phase 2 dose finding study, which included doses not expected to be effective, identified a potential reduction in congestive heart failure admissions in the AC6-treated group one year after randomization. The FLOURISH study is designed to investigate the prospect of reduction of heart failure hospitalization and other clinical adverse events and improvement in EF. The FLOURISH study is a double-blind, placebo-controlled, multicenter Phase 3 clinical trial that will randomize 536 patients to a one-time IC administration of RT-100 (1012 vp) or placebo in a 1:1 ratio. Subjects will be 18-80 years of age, on optimal standard of care HF therapy with LVEF ≥10% and ≤35% by echocardiogram, and will undergo IC administration of RT-100 vs. placebo on Day 1. Follow-up study visits will be performed at Weeks 1 and 4, and Months 3, 6, and 12. Patients will be followed for an additional 36 months for safety assessments with telephone contact at Months 24, 36, and 48. The primary objective is to determine the efficacy of IC RT-100 vs. placebo in reducing the event rate of all (first and repeat) HF hospitalizations occurring from baseline to 12 months. The secondary objectives are to determine the efficacy of IC RT-100 on CV death, all cause death, and all HF events and in improving NYHA functional classification. Exploratory endpoints will include echocardiographic parameters of left ventricular systolic and diastolic function, HF symptoms and physical limitations, 6-minute walking distance, Borg dyspnea score, and NT-proBNP levels. The FLOURISH study, which received fast track designation from the Food and Drug Administration in December 2017, will further investigate the role of a one-time intracoronary injection of RT-100 in reducing HF hospitalizations and will serve as a registration trial (potentially pivotal investigation) for RT-100 as a treatment for HFrEF.

ImportanceGene transfer has rarely been tested in randomized clinical trials.ObjectiveTo evaluate the safety and efficacy of intracoronary delivery of adenovirus 5 encoding adenylyl cyclase 6 (Ad5.hAC6) in heart failure.Design, setting, and participantsA randomized, double-blind, placebo-controlled, phase 2 clinical trial was conducted in US medical centers (randomization occurred from July 19, 2010, to October 30, 2014). Participants 18 to 80 years with symptomatic heart failure (ischemic and nonischemic) and an ejection fraction (EF) of 40% or less were screened; 86 individuals were enrolled, and 56 were randomized. Data analysis was of the intention-to-treat population. Participants underwent exercise testing and measurement of left ventricular EF (echocardiography) and then cardiac catheterization, where left ventricular pressure development (+dP/dt) and decline (-dP/dt) were recorded. Participants were randomized (3:1 ratio) to receive 1 of 5 doses of intracoronary Ad5.hAC6 or placebo. Participants underwent a second catheterization 4 weeks later for measurement of dP/dt. Exercise testing and EF were assessed 4 and 12 weeks after randomization.InterventionsIntracoronary administration of Ad5.hAC6 (3.2 × 109 to 1012 virus particles) or placebo.Main outcomes and measuresPrimary end points included exercise duration and EF before and 4 and 12 weeks after randomization and peak rates of +dP/dt and -dP/dt before and 4 weeks after randomization. Fourteen placebo participants were compared (intention to treat) with 24 Ad5.hAC6 participants receiving the highest 2 doses (D4 + 5).ResultsFifty-six individuals were randomized and monitored for up to 1 year. Forty-two participants (75%) received Ad5.hAC6 (mean [SE] age, 63 [1] years; EF, 30% [1%]), and 14 individuals (25%) received placebo (age, 62 [1] years; EF, 30% [2%]). Exercise duration showed no significant group differences (4 weeks, P = .27; 12 weeks, P = .47, respectively). The D4 + 5 participants had increased EF at 4 weeks (+6.0 [1.7] EF units; n = 21; P

Methods commonly used clinically to assess cardiac function in patients with heart failure include ejection fraction (EF), exercise treadmill testing (ETT), and symptom evaluation. Although these approaches are useful in evaluating patients with heart failure, there are at times substantial mismatches between individual assessments. For example, ETT results are often discordant with EF, and patients with minimal symptoms sometimes have surprisingly low EFs. To better define the relationship of these methods of assessment, we studied 56 patients with heart failure with reduced EF (HFrEF) who underwent measurement of ETT duration, EF by echocardiography, quantitative symptom evaluation, and LV peak dP/dt (rate of left ventricular pressure development and decline, measured invasively). Correlations were determined among these four tests in order to assess the relationship of EF, ETT, and symptoms against LV peak dP/dt. In addition, we sought to determine whether EF, ETT, and symptoms correlated with each other. Overall, correlations were poor. Only 15 of 63 total correlations (24%) were significant (p < 0.05). EF correlated most closely with LV peak -dP/dt. Linear regression analysis indicated that EF, ETT, and symptoms taken together predicted LV peak dP/dt better than any one measure alone. We conclude that clinical tests used to assess LV function in patients with HFrEF may not be as accurate or correlate as well as expected. All three clinical measures considered together may be the best representation of cardiac function in HFrEF patients currently available.

Objectives: We evaluated the efficacy and safety of prasugrel and clopidogrel in the setting of a glycoprotein (GP) IIb/IIIa inhibitor.Background: Prasugrel reduced cardiovascular events as compare...

Geographical Differences in the Rates of Angiographic Restenosis and Ischemia-Driven Target Vessel Revascularization After Percutaneous Coronary Interventions: Results From the Prevention of Resten...

Objectives The aim of the present study was to determine the rates of target vessel revascularization (TVR) and to determine predictors of TVR from clinical and angiographic variables available in the Prevention of Restenosis With Tranilast and its Outcomes (PRESTO) database. Background The rates of TVR after percutaneous revascularization procedures, and its prediction with available clinical and angiographic variables, is less well known. Methods We studied nine-month TVR in 11,484 patients enrolled in the PRESTO trial. Clinical, lesion-related, and procedural characteristics were analyzed in a logistic regression model. Study data were divided at random into an 80% training set on which the models were developed and a 20% hold-out set on which the model properties were evaluated. Results A total of 14% (n = 1,609) had ischemic TVR. Clinical variables with increased risk for TVR included younger age; hypertension; diabetes mellitus; nonsmokers; unstable angina; previous coronary artery bypass grafting; peripheral vascular disease; procedure- and lesion-related such as ostial location, multilesion angioplasty, location in the left anterior descending artery, length ≥20 mm, in-stent restenosis at baseline, and use of rotablator. There was significant increase in the risk of ischemic TVR at U.S. treatment sites. Smoking and stent placement were associated with lower risk of ischemic TVR. The mean area (± SD) under the receiver-operating characteristic curve of the bootstrap samples was 0.66, indicating a modest ability of the model to discriminate patients who needed TVR on follow-up. Conclusions Despite being the largest prospective trial designed to test restenosis, the discriminatory ability of the clinical and angiographic variables to predict TVR is modest.

Anginal symptoms due to myocardial ischemia continue to affect millions of patients despite ongoing improvements in the diagnosis and treatment of coronary artery disease. Revascularization therapy with percutaneous coronary interventions and coronary artery bypass graft surgery can be highly effective in eligible subjects, but many patients are suboptimal candidates due to various factors, which include diffuse vascular disease, poor ventricular function and failure of prior procedures. Introduction of vascular growth factors to the heart to promote angiogenesis and collateral vessel formation has emerged as an alternative strategy for the relief of myocardial ischemia in these patients. Early preclinical work demonstrated that gene transfer of fibroblast growth factor using an E1-deleted adenovirus vector via intracoronary injection could safely reverse stress-induced ischemic ventricular dysfunction with no discernible evidence of inflammatory response. The AGENT trial established that intracoronary administration of Ad5FGF-4 could be performed with reasonable safety to patients with coronary artery disease, and that a one-time dose could provide an anti-ischemic effect out to 12 weeks of evaluation. Further evaluation of the efficacy and safety of Ad5FGF-4 is now being conducted in two simultaneous multicenter, randomized, double-blind, placebo-controlled pivotal trials in the United States and the European Union, with planned enrollment of approximately 1000 treated subjects. The primary efficacy variable in the trial will be changed in treadmill exercise duration at 12 weeks compared to baseline. Secondary efficacy variables include the rate of all-cause mortality and coronary events (non-fatal myocardial infarction, and unplanned hospitalization and revascularization due to myocardial ischemia) up to 1 year.

The Symmetry Bypass Connector (St. Jude Medical, St. Paul, Minnesota) is a nitinol, star-shaped device that was designed to facilitate placement of sutureless aorto-saphenous anastomoses during off-pump coronary artery bypass graft surgery (CABG). Although the device is approved for clinical use in Europe and the U.S., its short- and long-term safety and efficacy are not established. We report on 5 of 121 patients undergoing CABG who presented with an acute coronary syndrome two to five months following placement of this device. In each patient, all saphenous vein grafts (SVGs) placed (n = 11) with the device were totally occluded (n = 6) or compromised by ostial stenoses (n = 5). Treatment consisted of repeat CABG in one patient and percutaneous coronary intervention (PCI) in four patients with cutting balloon atherotomy and stenting. Following PCI, two of four patients presented again within two months with near-occlusive ostial restenosis in all stents placed. Intracoronary ultrasound showed severe neointimal hyperplasia, but only at the proximal interface of the device and stent. One patient was treated with brachytherapy in two SVGs but had a recurrence four months later and was treated with drug-eluting stents in both restenotic segments. Recalcitrant neointimal hyperplasia is postulated to be involved in the pathogenesis of anastomotic device stenosis, possibly similar to in-stent restenosis. Prospective randomized clinical trials are needed to assess the clinical safety and efficacy of this device. Pending such studies, consideration should be given in limiting its use to cases of unacceptably high risk of stroke during aortic cross-clamping. Dual antiplatelet agents, evaluation for ischemia, and close follow-up are warranted in patients that have already received the device.

The patient is an 86-year-old man who presented to the hospital with 4 h of retrosternal chest pain and an anterior ST-segment elevation myocardial infarction on electrocardiogram. His past medical history included pulmonary sarcoidosis, a bioprosthetic aortic valve implanted in 1997, and long

OBJECTIVESThis study assessed coronary artery endothelial function in patients with hypercholesterolemia before and after lipid lowering, using quantitative angiography to examine the acetylcholine (Ach) response along the entire analyzable vessel.BACKGROUNDLipid lowering reverses endothelial dysfunction, but whether improvement occurs only in some segments and not others has not been established. Statistical correlation of improvement with specific lipid moieties remains undefined.METHODSQuantitative angiography was performed after Ach (10−6, 10−5, 10−4M) in 29 patients with coronary atherosclerosis before and 18 ± 5.2 months after lipid-lowering treatment (statins, bile sequestrant resins). Standard lipid moieties and markers of oxidized low density lipoprotein (LDL) (immunoglobulin G and M autoantibody titers to malondialdehyde-LDL, E06 epitope) were measured serially.RESULTSPre-treatment of the vessel diameters at control and with 10−6M, 10−5M and 10−4M Ach were 2.108 ± 0.085, 2.086 ± 0.087, 2.069 ± 0.084 and 1.963 ± 0.097 mm (M ± SE), respectively, and increased at follow-up to 2.139 ± 0.094, 2.119 ± 0.086, 2.127 ± 0.084 and 2.080 ± 0.085 mm (p < 0.0001). Improvement in the most constricted and modest declination in the more dilated segments were observed. Change in the E06 and Apolipoprotein A-1 titers correlated with improved vasomotion (p = 0.027 and 0.005, respectively). The pre- and post-treatment levels of the E06 epitope, as well as the post-treatment IgM autoantibody titer to MDA-low density lipoprotein, also correlated (p < 0.028, < 0.001 and p < 0.004, respectively).CONCLUSIONSDrug treatment reverses endothelial dysfunction, but the effect is heterogeneous. Most coronary segments show enhancement, while others show declination of dilation, underscoring the importance of assessing the entire analyzable artery. Improvement in vasomotion correlates most significantly with markers of plasma-oxidized low-density lipoprotein.

Background: Motion of the intravascular ultrasound (IVUS) probe within the coronary artery from cardiac contraction may result in artifacts during 3-dimensional ultrasound image reconstruction and inaccurate measurements of coronary compliance. The purpose of this study was to establish whether longitudinal movement of the IVUS transducer in the coronary artery occurs and to quantify such motion. Methods: In 31 patients we positioned IVUS transducers at 59 coronary branch points: 41 in the left anterior descending coronary artery, 11 in the left circumflex coronary artery, and 7 in the right coronary artery. In each image sequence the branching vessel oscillated in and out of the imaging plane during the cardiac cycle, confirming longitudinal transducer movement. The extent of movement was estimated by IVUS from the dimension of the branch vessel traversed. In addition, angiographic visualization and measurement of IVUS probe motion was performed at 17 branch points in 12 patients. Results: Average longitudinal transducer movement as measured by IVUS was 1.50 ± 0.80 mm (n = 46, range 0.5 to 5.5 mm). Because IVUS could not account for probe motion that exceeded the vessel branch diameter, the values obtained represent minimum movement. Average probe motion as assessed by cineangiography in a subset of 12 patients was 2.43 ± 1.42 mm (range 0.57 to 6.56 mm). Conclusions: This study establishes that longitudinal movement of IVUS transducers within coronary vessels occurs during the cardiac cycle. Because documented extent of motion may be sufficient to influence analysis, IVUS images are best obtained with electrocardiographic gating. (Am Heart J 1999;138:865-72.)

The increase in minimum lumen diameter achieved by coronary stent placement can be further enhanced by reducing the immediate recoil that occurs after stent deployment. The effect of various stent designs-flexible coils, slotted tubes, and a locking stent-on minimization of postdilation stent recoil was evaluated using an in vitro model of circumferential compression. The stents were expanded to 7 atm (3.82 +/- 0.02 mm); as pressure was reduced, lumen diameter and cross-sectional area (CSA) were determined by on-line intravascular ultrasound imaging (30 MHz) positioned inside the dilating balloon (n = 10-15 inflation-deflation cycles). Stent recoil was assessed by calculation of percent change in CSA from 7 atm to negative balloon pressure: -33.1 +/- 5.6% (GR-II) and -22.4 +/- 3.8% (Wiktor) in the coil stents; -20.0 +/- 4.2% (JJIS coronary), -8.4 +/- 2.6% (JJIS biliary), and -6.9 +/- 1.5% (Multilink) in the slotted tube stents; and -1.9 +/- 3.2% in the Navius ZR1 locking stent (P < 0.05 vs. Multilink, P < 0.0001 vs. others). A range of resistances to recoil is demonstrated by this model, with coil stent designs undergoing greater elastic recoil than slotted tube stent designs. The locking stent design demonstrated the greatest radial strength and the most reduction in elastic recoil.

Objectives. In view of the segmental occurrence of coronary atherosclerosis, we postulated that acetylcholine may cause heterogeneous vasomotion, depending on the extent of vessel analyzed, criteria for change in vessel caliber and dose of drug administered. Background. Previous studies have reported that acetylcholine causes constriction of atherosclerotic arteries. This dysfunction of endothelium-dependent dilation may be seen without angiographically detectable disease. Methods. We developed algorithms to quantitate the dimensions of a single coronary artery over virtually its entire length during a control state and during graded doses of intracoronary acetylcholine. On the basis of triplicate control angiograms, the limit of detection of a change from control diameter was 0.31 mm (≥2 SD). Results. Analysis of multiple segments (each 5.6 ± 1.1 [mean ±SD]mm) along a single coronary artery revealed a heterogeneous response to acetylcholine in 27 of 31 patients at the 10−4mol/liter dose and in 29 of 31 patients when responses at 10−6, 10−5and 10−4mol/liter doses were combined; in this latter analysis, constriction and dilation in the same vessel occurred in 45% of the patients. With acetylcholine, most of 349 segments demonstrated no change, but the greatest frequency of vasoconstriction (24.6%) and vasodilation (6.9%) was seen at the 10−4mol/liter dose. Inducible vasomotion was observed as far distally as 7.3 cm from the site of acetylcholine infusion. Conclusions. Response to intracoronary acetylcholine with mild coronary disease is heterogeneous; disparate dimensional responses may occur in different segments of the same vessel. Inclusion of all analyzable regions of a coronary artery and the use of a reproducibility limit for quantitative angiography are optimal for assessment of segmental coronary vasomotion.

Objectives: To evaluate the clinical outcomes in patients with chronic renal insufficiency (CRI) who undergo saphenous vein graft (SVG) intervention with drug-eluting stents (DES). Background: Patients with CRI have higher rates of major adverse cardiac events (MACE) after percutaneous revascularization. SVG intervention is associated with increased rates of MACE compared with percutaneous revascularization of native arteries. However, the impact of CRI on SVG intervention with DES has not been well delineated. Methods: Consecutive patients who underwent SVG intervention with DES at five medical centers from April 2003 to December 2007 were included in this analysis. Results: A total of 172 patients, 39 patients with CRI and a serum creatinine ≥1.5 mg dL−1, and 133 patients without CRI, underwent SVG intervention with DES. Patients with CRI were more often older, diabetic, and had a longer mean total stent length. At 1 year, patients with CRI had a higher MACE rate (35.9% vs. 15.8%, hazard ratio [HR] 2.48, 95% confidence interval [CI] 1.26–4.88, log rank P = 0.009), mainly driven by higher mortality (20.5% vs. 9.8%, HR 3.41, 95% CI 1.10–10.58, log rank P = 0.024). There was a trend toward higher rates of target vessel revascularization in the CRI group (21.8% vs. 10.3%, HR 2.42, 95% CI 0.94–6.24, log rank P = 0.059). Stent thrombosis rates were not different between patients with and without CRI (2.6% vs. 2.3%, P = 0.8). Multivariable analysis revealed that CRI was the only significant predictor of 1-year MACE (HR 2.2, 95% CI 1.1–4.3; P = 0.03). Conclusions: Patients with CRI who underwent SVG intervention with DES had higher risks of MACE and death compared with patients with preserved renal function. Further treatment strategies are needed in this high-risk group who undergo SVG intervention with DES. © 2010 Wiley-Liss, Inc.

This study was designed to compare the safety and efficacy of sirolimus-eluting stents (SESs) to paclitaxel-eluting stents (PESs) in percutaneous intervention of saphenous vein graft (SVG) lesions. SVGs develop atherosclerosis at high rates and often require repeat revascularization. Percutaneous intervention with drug-eluting stents has become the preferred method of revascularization due to higher restenosis with bare metal stents and increased morbidity and mortality with repeat coronary artery bypass grafting. We sought to compare the rate of major adverse cardiac events and stent thrombosis between SESs and PESs in patients undergoing SVG intervention. A multicenter analysis of 172 patients with SVG lesions treated with SESs or PESs was performed. The 30-day and 1-year clinical outcomes of 102 patients receiving SESs were compared to those of 70 patients receiving PESs. There was no significant difference in baseline demographic, angiographic, and procedural characteristics between the SES and PES treatment groups. There was no statistical difference in major adverse cardiac events at 30 days and at 1 year (hazard ratio [HR] 1.58, 95% confidence interval [CI] 0.77 to 3.23, log-rank p = 0.21). There was also no difference in survival (HR 1.28, 95% CI 0.39 to 4.25, log-rank p = 0.69) or target vessel revascularization (HR 2.54, 95% CI 0.84 to 7.72, log-rank p = 0.09). In conclusion, this multicenter analysis of real-world patients demonstrated that SESs and PESs have similar clinical outcomes when used in SVG intervention.

We evaluated the efficacy and safety of prasugrel and clopidogrel in the setting of a glycoprotein (GP) IIb/IIIa inhibitor.Prasugrel reduced cardiovascular events as compared with clopidogrel in TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction 38) but with increased bleeding.Researchers in the TRITON-TIMI 38 randomized 13,608 subjects with acute coronary syndrome undergoing percutaneous coronary intervention to prasugrel versus clopidogrel. The use of a GP IIb/IIIa inhibitor was at the physician's discretion. For the current analysis, end points were examined at 30 days and were stratified by use of a GP IIb/IIIa inhibitor.A total of 7,414 subjects (54.5%) received a GP IIb/IIIa inhibitor during their index hospitalization. There was a consistent benefit of prasugrel over clopidogrel for reducing cardiovascular death, myocardial infarction, or stroke in patients who did (hazard ratio: 0.76; 95% confidence interval: 0.64 to 0.90) or did not receive a GP IIb/IIIa inhibitor (hazard ratio: 0.78; 95% confidence interval: 0.63 to 0.97, p(interaction) = 0.83). Prasugrel significantly reduced myocardial infarction, urgent revascularization, and stent thrombosis irrespective of GP IIb/IIIa inhibitor use. Although subjects treated with a GP IIb/IIIa inhibitor had greater rates of bleeding, the risk of Thrombolysis in Myocardial Infarction major or minor bleeding with prasugrel versus clopidogrel was not significantly different in patients who were or were not treated with GP IIb/IIIa inhibitor (p(interaction) = 0.19).Prasugrel significantly reduces the risk of cardiovascular events in patients with acute coronary syndromes after percutaneous coronary intervention regardless of whether or not a GP IIb/IIIa inhibitor is used. The use of a GP IIb/IIIa inhibitor does not accentuate the relative risk of bleeding with prasugrel as compared with clopidogrel.

Hemodynamic stress testing was performed in four calves with a chronically implanted left ventricular assist device consisting of a double-valved pump interposed between the left ventricular apex and the descending thoracic aorta. The device was powered either pneumatically (n = 1) or with a transcutaneous energy transmission system (n = 3). Hemodynamic evaluation (cardiac output and right and left ventricular and pulmonary and carotid artery pressures) was carried out at baseline and during all hemodynamically stressed states. Atrial pacing and ventricular pacing to a heart rate of 140 beats/min resulted in no significant change in right or left heart filling pressures or cardiac output. Preload reduction with nitroprusside or transient inferior vena cava balloon occlusion resulted in a marked decrease in left ventricular pressure with preservation of mean arterial pressure. Phenylephrine administration resulted in a marked rise in mean arterial pressure with no change in cardiac output or filling pressure. Induction of ventricular fibrillation resulted in a decrease of mean left ventricular pressure to 11 +/- 8 mm Hg, but mean arterial pressure was maintained at greater than or equal to 50 mm Hg. It is concluded that a multicomponent, implantable, electrically powered assist system is capable of maintaining a normal cardiac output under a wide range of loading conditions and chronotropic states. Although this device is clearly preload dependent, it is capable of maintaining normal systemic pressures during conditions of severe left ventricular dysfunction and circulatory collapse.

Aim: Advanced age and female gender are both independent predictors of early and late mortality and adverse cardiac outcomes for patients undergoing balloon angioplasty. Elderly women are at particular risk. Stenting is now the standard of care in PCI. Whether elderly women remain at increased risk after PCI in the current stent era has not been examined widely. Methods: Prospective data were collected in 400 consecutive female patients undergoing PCI at a tertiary cardiac center (1999–2003). Follow-up was done at 1 month, 6 months, and 12 months by clinic visits, telephonic interviews, and reviewing hospital records. Follow-up was complete in 396 patients. Results: Compared to young women ( 65 years old) were less likely to smoke (15.7% vs 47.2%, P = 0.001), less likely to have diabetes (4.1% vs 8.5%, P = 0.05), and had more multivessel coronary artery disease. Usage of stent was high, similar in both groups. Hypertension, hypercholesterolemia, previous MI, vessels treated, abciximab usage, and access site bleeding were similar in both groups. Procedural success (96% vs 98%) and in-hospital and 1-year MACE (23.1% vs 25%) are similar in both groups. Conclusion: Elderly women undergoing PCI have a distinct profile presenting with more multivessel disease, less smoking, and are less likely to have diabetes than younger women. In the current stent era, procedural success, in-hospital adverse cardiac events, and MACE at 1 year are similar in both groups. At 1 year, however, elderly women are less likely to have ischemia-driven TVR and recurrence of angina.

ObjectivesThis study sought to determine the factors associated with suboptimal platelet inhibition (PI) with single- and double-bolus eptifibatide during percutaneous coronary intervention (PCI).BackgroundAlthough PI ≥ 95% measured 10 min after glycoprotein IIb/IIIa inhibitor therapy is associated with improved outcomes following PCI, this level of PI often is not achieved.MethodsWe prospectively studied 150 patients undergoing PCI with single-bolus eptifibatide (180 μg/kg) (n = 100) and double-bolus eptifibatide (180 μg/kg administered 10 min apart) (n = 50) followed by standard infusion (2 μg/kg/min). Measuring platelet aggregation at baseline and at 10 min and 30 to 45 min after eptifibatide bolus, patients were classified as optimal responders (OPT) (≥95% PI) or suboptimal responders (sub-OPT) (375 mg/dl is a strong predictor of suboptimal PI.

Many cardiologists consider it reasonable to assume in clinical practice that percutaneous coronary intervention using drug-eluting stents ought to be considered equivalent, if not superior, to bypass surgery. In the absence of a definitive clinical trial to support this view, how should the prudent, cutting-edge cardiologist proceed?This study assessed the geographical differences in target vessel revascularization (TVR) after percutaneous coronary intervention (PCI) in the Prevention of Restenosis With Tranilast and its Outcomes (PRESTO) trial.An aggressive approach to PCI is more common in the U.S. than in other countries. The impact of this approach on restenosis outcomes has not been studied.Using the PRESTO trial, we compared nine-month ischemic TVR after PCI in U.S.-treated patients (n = 5,026) with rates in other countries (n = 6,458). We defined TVR as repeat intervention for chest pain/positive stress test. Additionally, angiographic restenosis (or =50% narrowing oror =50% loss of gain at nine-month follow-up) was compared between U.S. and non-U.S. patients within the prespecified angiographic subset (n = 2,823). Regression models were developed to adjust for clinical and lesion-related characteristics.Higher rates of TVR (18% vs. 11%), and angiographic restenosis (65% vs. 48%) were observed in patients treated in the U.S. as compared with the other patients (p0.01 for both comparisons). Patients treated in the U.S. were more likely to be female, diabetic, not currently smoking, to have unstable angina, and to have a prior PCI. In U.S. patients, lesions tended to be longer, but less likely to be American College of Cardiology/American Heart Association class C. After adjusting for clinical and angiographic variables, PCI in the U.S. was still associated with increased angiographic restenosis and ischemic TVR.Angiographic restenosis and ischemia-driven TVR rates were higher in patients treated in the U.S. The difference could only partially be explained by the higher prevalence of measured adverse clinical and angiographic features.

Background— Restenosis prediction from published studies is hampered by inadequate sample size and incomplete angiographic follow-up. The prediction of restenosis with the existing variables is poor. The aim of the present study was to include the clinical and angiographic variables commonly associated with angiographic restenosis and develop a prediction model for restenosis from the PRESTO database. Methods and Results— This study included 1312 patients with a single lesion enrolled in the angiographic substudy of the PRESTO trial. We constructed 2 risk scores. The first used preprocedural variables (female gender, vessel size [≤2.5 mm, 2.5 to 3 mm, 3 to 3.5 mm, 3.5 to 4 mm, >4 mm], lesion length >20 mm, diabetes, smoking status, type C lesion, any previous percutaneous coronary intervention [PCI], and unstable angina) derived from previous studies. Estimated restenosis rates and corresponding variability for each possible level of the resultant risk score were obtained via bootstrapping techniques. The area under the receiver-operator characteristic (ROC) curve was 0.63, indicating modest discriminatory ability to predict restenosis. The second approach constructed a multiple logistic regression model considering significant univariate clinical and angiographic predictors of restenosis identified from the PRESTO database (treated diabetes mellitus, nonsmoker, vessel size, lesion length, American College of Cardiology/American Heart Association type C lesion, ostial location, and previous PCI). The area under the ROC curve for this risk score was also 0.63. Conclusions— The preprocedural clinical and angiographic variables from available studies and from the PRESTO trial have only modest predictive ability for restenosis after PCI.

The Symmetry Bypass Connector (St. Jude Medical, St. Paul, Minnesota) is a nitinol, star-shaped device that was designed to facilitate placement of sutureless aorto-saphenous anastomoses during off-pump coronary artery bypass graft surgery (CABG). Although the device is approved for clinical use in Europe and the U.S., its short- and long-term safety and efficacy are not established. We report on 5 of 121 patients undergoing CABG who presented with an acute coronary syndrome two to five months following placement of this device. In each patient, all saphenous vein grafts (SVGs) placed (n = 11) with the device were totally occluded (n = 6) or compromised by ostial stenoses (n = 5). Treatment consisted of repeat CABG in one patient and percutaneous coronary intervention (PCI) in four patients with cutting balloon atherotomy and stenting. Following PCI, two of four patients presented again within two months with near-occlusive ostial restenosis in all stents placed. Intracoronary ultrasound showed severe neointimal hyperplasia, but only at the proximal interface of the device and stent. One patient was treated with brachytherapy in two SVGs but had a recurrence four months later and was treated with drug-eluting stents in both restenotic segments. Recalcitrant neointimal hyperplasia is postulated to be involved in the pathogenesis of anastomotic device stenosis, possibly similar to in-stent restenosis. Prospective randomized clinical trials are needed to assess the clinical safety and efficacy of this device. Pending such studies, consideration should be given in limiting its use to cases of unacceptably high risk of stroke during aortic cross-clamping. Dual antiplatelet agents, evaluation for ischemia, and close follow-up are warranted in patients that have already received the device.

Despite utilizing optimal anticoagulant therapy during percutaneous coronary intervention (PCI), the incidence of periprocedural myocardial infarction (PPMI) remains 5 7% and evaluation of preprocedural clinical/angiographic characteristics has failed to reliably predict the likelihood of a PPMI. We hypothesized that immediate post-PCI assessment could identify a group of patients at very low risk for PPMI. A consecutive series of 258 PCI patients was stratified into 3 groups based on immediate post-PCI assessment. Group I (PPMI not expected) included those with an acceptable angiographic result of treated vessel (residual stenosis50%), TIMI 3 flow and absence of any intraprocedural complications. Group II (PPMI not unexpected) included those with an acceptable angiographic result, TIMI 3 flow but with any/all of the following: saphenous vein graft (SVG) PCI, transient closure of culprit vessel or major sidebranch, intracoronary thrombus, prolonged chest pain, electrocardiographic (ECG) changes, hypotension, resolved slow flow/no reflow, bailout glycoprotein IIb/IIIa inhibitor use, loss of a minor sidebranch or any angiographic residual stenosis50% with TIMI 3 flow. Group III (PPMI expected) included those with any angiographic result of native coronary artery or SVG withTIMI 3 flow, unresolved chest pain, hypotension or ECG changes at the end of the PCI, loss of a major sidebranch or vessel, or persistent no-reflow. Group stratification was analyzed in relation to the incidence of PPMI (CK-MB3 times the upper limit of normal; 18 24 hours post-PCI). Rate of PPMI: Group I (1/141; 0.7%), Group II (7/71; 9.9%), Group III (5/11; 45.5%) (p0.001). The 3 groups did not differ in age, clinical presentation or stent use (p = NS). Sixty out of 105 patients (57.1%) with unstable angina, seventy-seven out of 146 patients (52.7%) with B2/C lesions, and 105/180 patients (58.3%) with unstable angina or B2/C lesions were stratified to Group I. This study demonstrates that immediate post-PCI evaluation of the clinical/angiographic characteristics can predict the likelihood of PPMI and a group of patients at a very low risk for a PPMI can be identified, in whom implications exist for limited hospitalization and post-procedural antithrombotic therapy.

Background — The angiogenic response to myocardial ischemia can be augmented in animal models by gene transfer with the use of a replication defective adenovirus (Ad) containing a human fibroblast growth factor (FGF) gene. Methods and Results — The objectives of the Angiogenic GENe Therapy (AGENT) trial were to evaluate the safety and anti-ischemic effects of 5 ascending doses of Ad5-FGF4 in patients with angina and to select potentially safe and effective doses for subsequent study. Seventy-nine patients with chronic stable angina Canadian Cardiovascular Society class 2 or 3 underwent double-blind randomization (1:3) to placebo (n=19) or Ad5-FGF4 (n=60). Safety evaluations were performed at each visit and exercise treadmill testing (ETT) at baseline and at 4 and 12 weeks. Single intracoronary administration of Ad5-FGF4 seemed to be safe and well tolerated with no immediate adverse events. Fever of P =NS, n=79). A protocol-specified, subgroup analysis showed the greatest improvement in patients with baseline ETT ≤10 minutes (1.6 versus 0.6 minutes, P =0.01, n=50). Conclusions — Results show evidence of favorable anti-ischemic effects with Ad5-FGF4 compared with placebo, and it appears to be safe. Angiogenic gene transfer with Ad5-FGF4 shows promise as a new therapeutic approach to the treatment of angina pectoris.

Performing percutaneous coronary intervention (PCI) through radial access has been demonstrated to be beneficial. Primary PCI (PPCI) is the standard of care in those presenting with ST elevation myocardial infarction (STEMI). Emerging data does suggest that performing PPCI through radial access

We appreciate Dr. Bach’s interesting comments regarding our study of the changes in coronary endothelial dysfunction occurring after lipid lowering [(1)][1]. We certainly agree that the segmental heterogeneity of these changes in response to acetlycholine suggests a level of complexity that has

In this issue of the Journal , Togni et al. ([1][1]) report that exercise-induced coronary vasomotion is abnormal in segments proximal and distal to sirolimus-eluting stents (SES) when evaluated six months after deployment. While subjects who had received bare-metal stents demonstrated normal

We report a case of intravascular ultrasound (IVUS) imaging of a chronic total coronary artery occlusion angioplasty initially complicated by subintimal wire penetration. IVUS provided unique images of wire position and a “double-barrel” lumen that complemented angiographic data in initial diagnosis and in subsequent guidance of the procedure. © 1995 Wiley-Liss, Inc.

BACKGROUND Valvular heart disease is associated with a decreased platelet circulating time and a thrombotic tendency. The possibility that these events are related to changes in von Willebrand factor (vWF), a multimeric glycoprotein released from endothelial cells and platelets that mediates platelet adhesion to the vascular subendothelium, has not been examined. METHODS AND RESULTS We measured the vWF antigen (vWF:Ag) concentration in 43 patients undergoing cardiac catheterization for the evaluation of mitral (n = 17) or aortic (n = 10) stenosis or nonvalvular heart disease (n = 16). Mean vWF:Ag concentration was significantly higher in patients with mitral stenosis than in those without (212 +/- 84 versus 150 +/- 79 units/dl, p less than 0.02); this elevation was associated with a significant elevation of pulmonary vascular resistance (PVR) in the patients with mitral stenosis (186 +/- 49 versus 133 +/- 81 dynes-sec-cm-5, p less than 0.02). The vWF:Ag levels in the entire group of patients (regardless of the presence or type of valvular disease) varied directly with PVR (r = 0.72, p less than 0.0001) and with pulmonary artery pressure (r = 0.60, p less than 0.0001) and inversely with cardiac output (r = 0.64, p less than 0.0001). Changes in PVR, pulmonary artery pressure, or cardiac output could not be correlated with circulating levels of fibrinogen or beta-thromboglobulin, which may be released from activated platelets, nor with the endothelial cell product tissue plasminogen activator. CONCLUSIONS The association of high vWF:Ag levels with increased PVR and decreased cardiac output in patients both with and without mitral stenosis suggests a hemodynamically induced increase in the endothelial release of vWF, which might contribute to a thrombotic tendency in these patients.