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Aims There are limited contemporary data on the use of initial fibrinolysis in ST‐segment elevation myocardial infarction cardiogenic shock (STEMI‐CS). This study sought to compare the outcomes of STEMI‐CS receiving initial fibrinolysis vs. primary percutaneous coronary intervention (PPCI). Methods Using the National (Nationwide) Inpatient Sample from 2009 to 2017, a comparative effectiveness study of adult (>18 years) STEMI‐CS admissions receiving pre‐hospital/in‐hospital fibrinolysis were compared with those receiving PPCI. Admissions with alternate indications for fibrinolysis and STEMI‐CS managed medically or with surgical revascularization (without fibrinolysis) were excluded. Outcomes of interest included in‐hospital mortality, development of non‐cardiac organ failure, complications, hospital length of stay, hospitalization costs, use of palliative care, and do‐not‐resuscitate status. Results During 2009–2017, 5297 and 110 452 admissions received initial fibrinolysis and PPCI, respectively. Compared with those receiving PPCI, the fibrinolysis group was more often non‐White, with lower co‐morbidity, and admitted on weekends and to small rural hospitals (all P

OBJECTIVES Coronary computerized tomography angiography (CCTA) is a rapidly emerging technology for the evaluation of chest pain in the emergency department (ED). We assessed trends in CCTA use and compared downstream healthcare utilization between CCTA and cardiac stress testing modalities. METHODS Using administrative claims data (Optum Labs Data Warehouse) from over 100 million geographically diverse privately insured and Medicare Advantage enrollees across the United States, we identified 2,047,799 ED patients from January 2006 to December 2013 who presented with chest pain and had a CCTA or cardiac stress test within 72 hours. Cohorts were established based on CCTA or functional stress testing (myocardial perfusion scintigraphy [MPS], stress echocardiogram [SE], or treadmill exercise electrocardiogram [TMET]) performed within 72 hours of the ED visit. We tracked subsequent invasive cardiac procedures (invasive coronary angiography [ICA], percutaneous coronary intervention [PCI], and coronary artery bypass grafting [CABG]), repeat noninvasive testing, return ED visits, hospitalization, and the rate of acute myocardial infarction (AMI) within 30 days. We used propensity-score matching to adjust for coronary artery disease (CAD) risk factors, Charlson-Deyo comorbidity index, and baseline differences between patients selected for CCTA or cardiac stress testing. Logistic regression was used to measure adjusted associations between testing modality and outcomes. RESULTS During the study period, CCTA use increased from 0.8% to 4.5% of all cardiac testing within 72 hours, a change of 434% (p-value for trend < 0.001), while rates of other cardiac stress testing modalities decreased (-22% for TMET [p < 0.001]; -11% for SE [p = 0.11]; -6% for MPS [p = 0.04]. After matching, there was no difference in the 30-day rate of AMI between testing modalities. Compared to MPS, CCTA was associated with higher rates of PCI (odds ratio [OR] = 1.25, 95% confidence interval [CI] = 1.04 to 1.51), and CABG (OR = 1.47; 95% CI = 1.03 to 2.13). Compared to SE and treadmill stress testing, CCTA was associated with more invasive procedures, hospitalizations, return ED visits, and repeat noninvasive testing. CONCLUSIONS CCTA use increased fourfold during the study period and was associated with higher rates of PCI, CABG, repeat noninvasive testing, hospitalization, and return ED visits. The authors have no relevant financial information or potential conflicts to disclose.

Objectives To investigate the utility and safety of the GuideLiner “mother-and-child” catheter system during transradial and transfemoral percutaneous coronary intervention (PCI). Background In patients with complex coronary anatomy, stent delivery can be challenging and result in procedural failure and complications. The GuideLiner is a coaxial guide extension system designed to enable deep vessel engagement and facilitate device delivery. The purpose of this study was to evaluate procedural success and safety in a series of GuideLiner-facilitated PCI. Methods Single center retrospective study of PCI utilizing the GuideLiner catheter between February 2010 and October 2014. Patients who underwent PCI without GuideLiner use during the same time period were used as controls for comparison. Results A total of 363 cases of GuideLiner-facilitated PCI were identified from 6,088 unique PCI procedures performed during this same time period. Patients in the GuideLiner group were older (mean age 71.5 vs. 67.8, P

Objectives To determine the feasibility of automated co-registration of angiography and intravascular ultrasound (IVUS) to facilitate integration of these two imaging modalities in a synchronous manner. Background IVUS provides cross-sectional imaging of coronary arteries but lacks overview of the vascular territory provided by angiography. Co-registration of angiography and IVUS would increase utility of IVUS in the clinical setting. Methods Forty-nine consecutive patients undergoing surveillance for cardiac allograft vasculopathy with angiography and IVUS of the left anterior descending artery (LAD) were enrolled. A pre-IVUS angiogram of the LAD was performed followed by an ECG-triggered fluoroscopy (ECGTF) during IVUS pullback at 0.5 mm/s using an automatic pullback device. ECGTF was used to track the IVUS catheter during pullback and establish a spatial relationship to the pre-IVUS angiogram. Angio-IVUS co-registration was performed with a research prototype (Siemens Healthcare, Germany) and accuracy was evaluated by distance mismatch between angiography and IVUS images at vessel bifurcations. Results Median age was 54 (44.5, 67) years. The population was 82.6% male with minimal risk factors. The median (IQR) co-registration distance mismatch measured at 108 bifurcations in 42 (85%) patients was 0.35 (0.00–1.16) mm. Seven patients were excluded due to inappropriate data acquisition (n = 3) and failure of tracking (n = 4), e.g., due to overlapping sternal wires. Estimated effective radiation dose for ECGTF was 0.09 mSv. Conclusion This study demonstrates the feasibility of angio-IVUS co-registration which may be used as a clinical tool for localizing IVUS cross-sections along an angiographic roadmap. © 2015 Wiley Periodicals, Inc.

Bridging for antiplatelet therapy remains a subject of debate with data favoring GP blockers but at a risk of bleeding. This Conversation in Cardiology addresses a key and often asked question about use of alternatives to P2Y12 agents in patients requiring surgery within 6 months after drug eluting stent implantation. © 2013 Wiley Periodicals, Inc.

Objective: To describe outcomes when glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors are used as bridging antiplatelet therapy for surgical procedures in patients with drug eluting stents (DES). Background: The optimal management of patients with DES who require surgical procedures prior to completion of antiplatelet therapy is unclear. In high risk patients, the use of GP IIb/IIIa inhibitors as bridging therapy while antiplatelet therapy is held has been described, but safety and efficacy data remain sparse. Methods: A pharmacy database was used to identify GP IIb/IIIa inhibitor orders at our hospital between January 1, 2007 and July 31, 2009. Indication for GP IIb/IIIa inhibitor administration and other clinical data were gathered through retrospective review of medical records. End points assessed were stent thrombosis, major bleeding, minor bleeding, postoperative acute coronary syndrome, and death within 30 days. Results: Four thousand One hundred seventy-six separate orders for GP IIb/IIIa inhibitors were identified (January 1, 2007 to July 31, 2009). Six patients underwent non-cardiac and thirteen underwent cardiac surgery. Clopidogrel was discontinued a median of 6 days before surgery and 2 days prior to initiating GP IIb/IIIa inhibitor. All bridging patients were treated with eptifibatide infusion prior to procedure. There were no stent thromboses, deaths, or acute coronary syndrome events. Major bleeding occurred in 7 (53.9%) cardiac surgery patients and none of the non-cardiac surgery patients, while minor bleeding occurred in 1 (7.7%) and 1 (16.6%) patients, respectively. Conclusions: In patients with DES, who require cessation of clopidogrel before surgery, bridging with GP IIb/IIIa inhibitors appears effective in preventing adverse cardiac outcomes but may be associated with bleeding in patients undergoing cardiac surgery. © 2011 Wiley Periodicals, Inc.

Objectives: We evaluated a sheathless transradial technique for interventions using standard five and six French nonhydrophilic guiding catheters. Background: Miniaturization of transradial interventions may serve to improve patient comfort and reduce the risk of access-site complications. Guiding catheters carry an outer diameter approximately 2 Fr sizes smaller than their corresponding introducer sheaths. Methods: We identified consecutive patients who underwent transradial intervention between August 2010 and December 2010 using 5 or 6 Fr guides with a sheathless technique. Results: A total of 11 patients were identified (mean age 70.7 ± 10.9 years; 73% male). Single coronary intervention was performed in 10 patients and renal artery intervention in one. Right radial access and 6 Fr guide catheters were used in the majority (each 73%). Five techniques were used to create an inner dilator as the taper. Four of these inner tapers (standard diagnostic catheters, hydrophilic diagnostic catheters, long sheath dilators and guide extensions) enabled successful sheathless guide insertion in all 10 patients attempted. One technique (a partially inflated angioplasty balloon protruding from the guide) attempted in one patient was unsuccessful. All interventional procedures were successful, there were no radial artery access-site complications and in no case was cross-over to femoral artery access-site required. Conclusion: Sheathless transradial intervention using standard 5 and 6 Fr guiding catheters is a safe and effective method for treatment of coronary and peripheral vascular lesions. © 2011 Wiley Periodicals, Inc.

The purpose of this study was to determine whether the unrestricted availability of intracoronary stents is affecting abrupt vascular closure rates and early clinical outcomes. Intracoronary stents have improved procedural outcome despite their application in more complex lesions, but the impact of unrestricted availability of stents on abrupt closure and early clinical outcomes is unknown. Two cohorts were identified retrospectively from a coronary intervention registry: patients treated between 1988 and 1992 (n = 3,617) when stents were not generally available, and patients treated between 1994 and 1997 (n = 4,518) when stents were freely available. The late cohort patients consisted of more females; it also had greater comorbidity and more complex presentation. However, there was a significant reduction in the abrupt closure rates between the two time periods (7% vs. 4%, P < 0.0001). After adjusting for female gender, thrombus, and lesion angulation, the late cohort remained significantly associated with decreased odds of abrupt closure (odds ratio [OR] = 0.62, 95% upper and lower confidence intervals [CI] = 0.52–0.75, P = 0.0001). The late cohort also had decreased in-hospital mortality (OR = 0.91, CI = 0.86–0.95, P = 0.0002) and major adverse clinical event (OR = 0.93, CI = 0.91–0.96, P = 0.0001). Unrestricted availability of intracoronary stents is associated with reduced abrupt closure rates and improved early clinical outcomes among patients undergoing coronary intervention despite treatment of high-risk patients. Cathet Cardiovasc Intervent 2002;55:294–302. © 2002 Wiley-Liss, Inc.

A large matched-cohort study was carried out to determine correlates of in-hospital abrupt vascular closure (AC). Univariate analysis identified current cigarette smoking (P = 0.021), myocardial infarction within 24 hr prior to procedure (P = 0.0035), emergency procedure (P = 0.02), lesion thrombus (P = 0.0001), and lesion angulation (P = 0.021) as significant clinical and angiographic variables. Relative to balloon angioplasty (PTCA), use of atherectomy (P = 0.015) and laser devices (P = 0.018) but not elective stent placement (P = 0.97) were associated with increased risk of AC. In the multivariate model, current cigarette smoking (P = 0.0474), lesion thrombus (P = 0.0001), lesion angulation (P = 0.0124), use of atherectomy devices (P = 0.001), and laser devices (P = 0.0037) remained as significant correlates of increased AC events. In conclusion, the risk of AC appears associated primarily with lesion characteristics and use of nonballoon devices other than stents. Elective stent placement did not appear to reduce AC risk over conventional PTCA; the small number of patients studied may have prevented any benefit from being observed.

The acceptance of the Digital Imaging and Communication in Medicine (DICOM) standard and the Compact Disk-Recordable (CD-R) as the interchange medium have been critical developments for laboratories that need to move forward on the cine replacement front, while at the same time retain a means to communicate with other centers. One remaining essential component which has not been satisfactorily addressed is the issue of how digital image data should be archived within an institution. Every laboratory must consider the diverse issues which affect the choice of a digital archiving system. These factors include technical and economic issues, along with the clinical routines prevailing in their laboratory. A complete understanding of the issues will lead to the formulation of multiple options which may prove acceptable and will help to overcome the last obstacle which remains for the complete replacement of cine film in the cardiac catheterization laboratory. Cathet. Cardiovasc. Diagn. 44:346–356, 1998. © 1998 Wiley-Liss, Inc.

Our objective was to document change in stent usage in a single practice over time and to study "off-label" compared to Food and Drug Administration (FDA)-approved indications. Although only two intracoronary stents have been approved by the FDA, the relatively limited approved indications do not account for the dramatic increase in stent implantation. This increase has important implications for patient health care delivery. This study of stent usage in a single center over a 36-mo period included all patients treated with coronary stents at the Mayo Clinic from January 1993-December 1995, and evaluated the relative difference in frequency between "off-label" and FDA-approved indications for implantation. During the 36-mo period of study, 3,614 interventional procedures were done and one or more stents were placed in 25.4% of patients. The proportion of patients receiving stents increased throughout this time: during the first 6-mo period, stents were placed in 6.2% of procedures; during the last 6-mo period, stents were placed in 46.3% of procedures, an eightfold increase. During the final 6 mo, an unapproved device or an unapproved indication for an approved device constituted 59.4% of all stent procedures. In addition, use of the non-FDA-approved adjunctive treatment regimen without warfarin increased from 2.9% in the first 6-mo period of observation to 82.7% in the last 6 mo. The use of stents increased strikingly over a 36-mo period, from 6% to 46% of all procedures. The majority of implantations were performed either for an "off-label" unapproved indication or with an unapproved device.

We describe a method of validation of computerized quantitative coronary arteriography and report the results of a new UNIX-based quantitative coronary arteriography software program developed for rapid on-line (digital) and off-line (digital or cinefilm) analysis. The UNIX operating system is widely available in computer systems using very fast processors and has excellent graphics capabilities. The system is potentially compatible with any cardiac digital x-ray system for on-line analysis and has been designed to incorporate an integrated database, have on-line and immediate recall capabilities, and provide digital access to all data. The accuracy (mean signed differences of the observed minus the true dimensions) and precision (pooled standard deviations of the measurements) of the program were determined x-ray vessel phantoms. Intra- and interobserver variabilities were assessed from in vivo studies during routine clinical coronary arteriography. Precision from the x-ray phantom studies (6-In. field of view) for digital images was 0.066 mm and for digitized cine images was 0.060 mm. Accuracy was 0.076 mm (overestimation) for digital images compared to 0.008 mm for digitized cine images. Diagnostic coronary catheters were also used for calibration; accuracy.varied according to size of catheter and whether or not they were filled with iodinated contrast. Intra- and interobserver variabilities were excellent and indicated that coronary lesion measurements were relatively user-independent. Thus, this easy to use and very fast UNIX based program appears to be robust with optimal accuracy and precision for clinical and research applications.

The immediate outcome of 271 procedures involving the intracoronary implantation of 305 stents was determined. Data were analyzed with regard to indication for stenting and stent size. Elective indication was associated with a higher success rate than emergency indication (95.6% vs. 86.6%, P = 0.013) and a lower Q-wave infarction rate (0 vs. 6.4%, P = 0.006). Univariate analysis showed that the odds ratio for procedural success was significantly favored by elective indication (3.37, P = 0.018) but was unrelated to stent size (1.10, P = 0.087). These findings were confirmed on multivariate analysis. The likelihood of Q-wave infarction was lower for elective placement (P = 0.0008) but was not related to size. Requirement for emergency bypass surgery, incidence of subacute closure, and death were not related to indication or to stent size on either univariate or multivariate analysis. Therefore, the immediate outcome of stent placement is related to the indication for stenting, but not to the size of stent implanted. Procedural success is significantly favored by elective indication.

Conventional coronary balloon angioplasty is complicated by abrupt arterial occlusion in 4%-8% of cases and remains the most important and feared acute problem with this procedure. This review discusses the significance and various treatment options for abrupt occlusion, focusing particularly on the potential use of directional coronary atherectomy to treat significant coronary arterial dissections complicating conventional angioplasty. The use of adjunctive atherectomy for the treatment of suboptimal coronary angioplasty results without dissection is also discussed. (J Interven Cardiol 1996;9:129–134)

Complex coronary disease may be defined as a disease in which one or more morphological features are present that are known to be associated with an increased risk of complications during angioplasty. Directional coronary atherectomy may be useful in treating such complex lesions. We review our experiences with complex coronary lesions treated with directional coronary atherectomy. Outcome data are presented within the context of the reported literature, and strategies for approaching complex disease with directional atherectomy are suggested. (J Interven Cardiol 1996;9:135–144)

A new method for the synthesis of 4-alky/aryl substituted saccharins (2) has been developed. The key steps include conjugate addition/acylation of cyclohexenone (3) and reaction of the resulting β-ketoesters 4 with benzyl mercaptan to give the vinyl sulfides 5 and 6. The latter were converted to the saccharins 2 in high yield.

Monofluoroacetyl and difluoroacetylsteroidal furans were prepared by selective reductive dehalogenation of chlorofluoro and chlorodifluoroacetyl intermediates with sodium formaldehyde sulfoxylate.

The lead compound for this SAR study, benzisothiazolone 1a, was a 15 nM inhibitor of HLE, but was unstable in human blood ( t 1 2 min). The introduction of lipophilic substituents at the R4-position such as ethyl or isopropyl and modulation of the electrophilicity of the benzisothiazolone carbonyl led to the identification of a potent ( K i ∗ =0.27 nM) and blood stable ( t 1 2 =260 min) inhibitor 2e, WIN 63395.

Indence analogs of pravadoline exhibited antinociceptive activity in several animal models. The inhibition of prostaglandin (PG) synthesis in mouse brain microsomes was diminished in these pravadoline analogs, but they were potent in inhibiting electrically stimulated contractions in the mouse vas deferens (MVD) preparations. Binding studies with ligand WIN 55212-2 have aided to demonstrate that the morpholinoalkyl-indene binding site is functionally equivalent with cannabinoid binding site. The antinociceptive activity of the indene derivatives appears to be mediated by increased affinity for the cannabinoid receptor.

This study compares the sensitivity and variability of four models of tau, the time constant of ventricular relaxation, to detect the presence of myocardial ischemia. High fidelity left ventricular pressure recordings were obtained in ten patients undergoing coronary angioplasty at baseline, during balloon inflation, and at recovery. Four models of tau were considered: (1) a semilogarithmic, zero asymptote model (TL), (2) a semilogarithmic model using data from the first 40 ms of isovolumic relaxation (T40), (3) an exponential non-zero asymptote model (Te), and (4) a derivative non-zero asymptote model (TD). TL, T40, and TE increased significantly during inflation and returned to near baseline values at recovery. TD showed no change during inflation. Comparisons of TL, T40, and TE using the derived relaxation half-time (T1/2), failed to reveal significant differences between the models at baseline, during inflation, or at recovery. The non-zero asymptote models were associated with a greater beat-to-beat variability than the semilogarithmic models. Thus, T1/2 using the semilogarithmic zero asymptote models (TL and T40) may be more useful and consistent when measuring the rate of isovolumic relaxation during myocardial ischemia.

Reaction of 17-oxoandrost-2,4-dieno[2,3-d]isoxazole with arylzirconium tributoxides gives the corresponding C-17 aryl carbinols. Arylzirconium tributoxides are selective nucleophiles towards readily enolizable 17-ketosteroids and are less basic than lithium and Grignard reagents

The cyclopenta[c]pyrrole-4-carbonitrile (3) is transformed by hyrlroxylamine in hot alcohol to 4,5,6,6a-tetrahydro-l-imino-3,5,5,6a-tetramethyl-4-cyclopenta[c]pyrrole methyl ketone oxime (5) in contrast to the cyclopentapyrrole 10 which afforded 1,2-diacetyl-3,3,5,5-tetramethyl-cyclopentene dioxime (11). The cyclopenta[c]pyrrole-4-carboxamide 1 (R = C6H5) yielded the isomeric 2a,3,4,4a,5,6,6a,6b-octahydro-2a,4,4,6a-tetramethyl-5-(phenylimino)pentaleno[1,6-bc]-pyrrol-2-(1H)one (12) in hot dilute hydrochloric acid or hot 99% phosphoric acid. The amide 1 (R = C6H5) was transformed in the solid state by oxygen over a period of several months to a mixture of the isomeric anils, 13 and 14 of 1,7-diacetyl-7-hydroxy-4,6,6-trimethyl-2-azabicyclo-[2.2.l.]heptan-3-one(16).

4-[(9-Methyl-as-triazino[6,5-b]indol-3-yl)amino]-2-methyl-2-butanol (13) and the corresponding 2-methyl-3-imino derivative 12 were synthesized and tested in vitro against Rhino 2 virus. The two compounds were more active than the known triazino[5,6-b]indole 4. 2,9-Dimethyl-3-methoxy-9H-as-triazino[6,5-b]indolium tosylate (21) and the related 3-methylthio compound 9 were prepared. Quaternary 21 formed a pseudo base, 22a, whereas quaternary 9 did not form a pseudo base.

Die Kondensation zwischen dem Oxazolon (I) und dem Thiazolin (II) fuhrt in Ge= . genwart von Pyridin zum Kondensat (III), das z.B. mit-p-Anisylalkohol zu (IVa) gespalten wird.

Condensation of a 1-substituted 2,5-dimethylpyrrole 6 with 2 mol of 2-amino-2-methylpropionitrile in hot acetic acid yielded a 2-substituted 2,4,5,6-tetrahydro-1,3,4,5,6,6-pentamethylcyclopenta[c]pyrrole-4-carbonitrile (4). Hydrolysis of the nitriles to the amides gave a group of compounds which were active as antisecretory agents in the pyloric-ligated rat. Outstanding in this respect was the 2-phenyl derivative 5b, the most active compound in the series. It did not possess anticholinergic properties. In contrast to the indoles and pyrroles reported earlier, 5b demonstrated marked activity in blocking gastric acid secretion in the histamine-stimulated dog.

The synthesis of 1,3-disubstituted 2,4,5,6-tetrahydro-4,6,6-trimethyl-2-phenylcyclopenta[c]pyrrole-4-carboxamides is reported. The derivatives included R1 = R3 = H, R1 = CH2OH with R3 = H (16) or CH3, R1 = CH3 with R3 = CH2OH (17), and R1 = R3 = CH2OH. The monohydroxymethyl derivatives were as active as the parent cyclopentapyrrole, where R1 = R3 = CH3 (1), when administered orally in the pyloric ligated rat. The compounds lacking one or both CH3 groups at C-1 or C-3 were much less active. Compounds 16 and 17 inhibited histamine-induced gastric acid secretion in the dog.

The synthesis and gastric antisecretory activity of a series of indole-1-alkanamides and pyrrole-1-alkanamides are presented. A marked elevation of the pH of the gastric secretions of the rat was observed after oral administration of 100 mg/kg of 2,3-dimethylindole-1-acetamide (2), -1-propionamide (8), and -1-butyramide (13). Replacement of either methyl group by a hydrogen atom or an ethyl radical resulted in greatly diminished activity. In the acetamide and propionamide series the 3-hydroxymethyl-2-methyl (14 and 15) derivatives exhibited activity but only when administered by the subcutaneous route. 2,3-Dimethylindole (18) was active and 2,3,4,5-tetramethylpyrrole-1-acetamide was moderately active. A number of the activ compounds were tested in the mouse mydriasis test for anticholinergic activity and found to be inactive. They were also found to be inactive in blocking histamine-induced acid secretion in the dog.