Search

A 79-year-old woman presented in cardiogenic shock with a flail bioprosthetic mitral valve leaflet and Staphylococcus aureus endocarditis. In the absence of other viable options, transfemoral valve-in-valve transcatheter mitral valve replacement was performed with a novel embolic protection device, resulting in trace mitral regurgitation and no neurologic complications. (Level of Difficulty: Advanced.), Graphical abstract, A 79-year-old woman presented in cardiogenic shock with a flail bioprosthetic mitral valve leaflet and Staphylococcus aureus endocarditis…

In Chaucer's Knight's Tale, chivalric heroism depends on a knight's ability to exercise both prowess and lordship. This article analyzes chivalry in Chaucer's romance alongside medieval didactic texts and modern historical discussions of the English nobility to suggest that the medieval imagination considered noble social status, and the personal control of men that status implied, to be an integral aspect of knighthood. As Theseus, Palamon, and Arcite call upon attendants in preparation for combat and prestigious displays, they demonstrate Chaucer's interest in interdependent relationships between noblemen and their supporters. The tale characterizes chivalry as an organizing principle that links men together with bonds of mutual loyalty.

Background Transcatheter aortic valve implantation (TAVI) is an alternative and effective contemporary intervention to surgical aortic valve replacement (SAVR) for patients with severe aortic valve disease at increased surgical risk. Guidelines recommend a multidisciplinary “Heart Team” (MHT) review of patients considered for a TAVI procedure, but this has been little studied. We reviewed the characteristics, treatments and outcomes of such patients reviewed by the MHT at our centre. Methods Data on consecutive patients with severe aortic valve stenosis discussed by the Auckland City Hospital MHT from June 2011 to August 2016 were obtained from clinical records. Patient characteristics, treatment and outcomes were analysed using standard statistical methods. Results Over the 5-year period 243 patients (mean age 80.2 ± 8.0 years, 60% male) were presented at the MHT meeting. TAVI was recommended for 200, SAVR for 26 and medical therapy for 17 patients, with no significant difference in mean age (80.2 ± 8.3, 80.4 ± 6.1, 80.4 ± 7.3 years, respectively) or EuroSCORE II (6.5 ± 4.7%, 5.3 ± 3.6%, 6.7 ± 4.3%, respectively). Over time, there was an increase in the number of patients discussed and treated, with no change in their mean age, but the mean EuroSCORE II significantly decreased (TAVI p = 0.026, SAVR p = 0.004). Survival after TAVI and SAVR was similar to that of the age-matched general population, but superior to medical therapy p = 0.002 (93% (n = 162), 84% (n = 21) and 73% (n = 18) at one year and 85% (n = 149), 84% (n = 21) and 54% (n = 13) at 2 years, respectively). Conclusions An increasing number of patients were discussed at the MHT meeting with the majority undergoing TAVI, with a similar age and EuroSCORE II to those allocated SAVR or medical therapy. Survival following TAVI and SAVR was superior to medical therapy and similar to the age-matched general population. These findings suggest that the MHT process is robust, consistent and appropriately allocating a limited treatment resource.

The facilities and expertise required for primary percutaneous coronary intervention (PPCI) of the infarct-related artery (IRA) in patients with ST-elevation myocardial infarction (STEMI) are only available at a limited number of hospitals. Fibrinolytic therapy, on the other hand, is more widely deliverable. This creates two distinct reperfusion choices: PPCI or a pharmacoinvasive strategy. The first option relies on immediate transfer to the closest PPCI-capable centre even if it means bypassing a closer non-PPCI centre. The second option is the “drip and ship” strategy. It involves delivery of fibrinolytic therapy by a non-PPCI facility with rapid transfer to a PPCI-capable centre.

The Cardiac Society of Australia and New Zealand (CSANZ) and the Australia and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) have joined together to provide recommendations for institutions and individual operators to assess their ability to initiate and maintain a transcatheter valve program. Transcatheter aortic valve replacement has been developed as an alternative to traditional surgical replacement of the aortic valve in high risk patients, particularly the frail elderly. The position paper has endorsed the important role of a multi-disciplinary "Heart Team" in selecting patients for TAVI as fundamental to the establishment of a successful program. The paper outlines recommendations for the cardiologist to have a background in structural intervention and the surgeon to have experience in high-risk aortic valve replacement. It is further recommended that TAVI programs be established in high volume cardiac surgical centres where on site valve surgery is performed. The paper is intended to provide guidance to individual operators and prospective institutions considering the establishment of a successful TAVI program.

This article positions Thomas Chestre's Sir Launfal alongside chivalric manuals and histories of nobility in order to highlight the ways in which a knight's attendants and companions support his heroism and social status. ( JTS)The knight in medieval England rarely worked alone. Whether he served under a magnate or at the head of a regiment, a knight was almost always a part of a much larger company of men. This is especially true of English knights of the later Middle Ages, whose social roles on and off the battlefield proliferated as time went on. Since at least the thirteenth century, responsibilities in town government kept knights occupied. As literacy spread among the members of England's landed class, so too did knowledge of legal and administrative matters, which allowed knights to serve their king as counselors and functionaries at court; by the middle of the fourteenth century, knights had begun to occupy government posts previously reserved for clerics.1 At home, knights also managed large households and directed many servants who helped maintain the impressive estates of the nobility. With the support of their stewards, many knights cultivated reputations for largess and even drew censure from Thomas Walsingham, who claimed that these nobles were forsaking their swords while training their tongues.2 But, although they took on responsibilities of management removed from battle, medieval knights were, and still are, largely defined through their most visible and spectacular role as bellatores-the armored, mounted warriors who fought for the king. Historians of chivalry have shown that knighthood was indelibly linked with armed combat through at least the end of the fourteenth century.3 And just as the knight's duties at court and at home required that he work as part of a governing body, so too was the knight on the battlefield one man among a company of men. The expansion of the knight's weaponry and armor in the later Middle Ages led to a parallel expansion in the knight's retinue, on whom he depended for support in battle. Even while a knight fought an opponent in single combat on the tournament grounds, a company of squires and attendants helped their employer to victory by looking after his horses, armor, and weapons.4The cooperation between knights, squires, and magnates appears in medieval chivalric manuals as a sign of proper noble behavior. Didactic texts by Ramon Llull in the thirteenth century and Geoffroi de Charny in the fourteenth emphasize knights' responsibility to uphold their own honor even while they also insist that the knights' duties often require working together with other members of the higher and lower nobility.5 These writers approach their pedagogical projects from different angles-Llull focuses heavily on symbolism and interpretation, Charny on more pragmatic concerns- but their texts concur when the writers tell their audiences how to avoid dishonorable behavior in ways that promote reciprocal support. Moreover, cooperation between nobles appears prominently in modern studies of chivalry and nobility.6 In light of the knight's cooperation with other nobles in late medieval England at war, in the household, and on the tournament grounds, it is surprising that a hero's companions should appear so seldom in discussions of the idealized chivalric romances of the time. Members of the English aristocracy had many opportunities to see large companies ride against each other in tournaments during the reign of Richard II, whose love of pageantry and extravagance led him to drain England's coffers in order to fund increasingly elaborate public displays of nobility.7 Nonetheless, Maldwyn Mills insists that chivalric romances center on 'the prowess and fortunes of individual knights, even when they also relate the activities of a large company of such knights at court.'8 Although knights under Richard II fought in immense groups, the romances of the late fourteenth century appear to focus instead on single combat and individual success. …

Cardiac troponins are the preferred biomarkers for diagnosing myocardial infarction (MI). High-sensitivity troponin T (hs-TnT) assays have increased sensitivity and enable more rapid diagnosis of infarction. We assessed the prognostic utility of admission hs-TnT to detect outcomes after primary angioplasty for ST-elevation/new left bundle branch block myocardial infarction (STEMI).Patients admitted to Auckland City Hospital for acute coronary catheterization with a diagnosis of STEMI between October 2010 and September 2011 were identified, and included if hs-TnT levels were measured at admission. Clinical characteristics and major adverse cardiovascular events (MACE: death, myocardial infarction and revascularization) at 30 days and 1 year were collected from national statistics and electronic medical records.Median admission hs-TnT level in the 173 STEMI patients studied was 59 ng/L (interquartile range (IQR) 19-310). Incidences of MACE at 30 days and 1 year were 10% (n=17) and 18% (n=31), respectively. C-statistics and 95% confidence interval (CI) (95% CI) for hs-TnT on admission at detecting MACE at 30 days and 1 year were 0.800 (0.696-0.904) and 0.750 (0.655-0.845) respectively, with the optimal cut-point of 225 ng/L giving sensitivities/specificities of 76.5%/75.6% and 64.5%/78.2% respectively. Admission log(hs-TnT) independently predicted both MACE at 30 days with hazards ratio 5.16, 95% CI (2.25-11.9) and 1 year with hazards ratio 2.88, 95% CI (1.79-4.63), as did age and cardiogenic shock. Age, Maori or Pacific ethnicity and chronic respiratory disease were independent predictors of hs-TnT225 ng/L.Admission hs-TnT measured in primary angioplasty is strongly prognostic of MACE at 30 days and 1 year, even following adjustment for potential confounding variables.

Hypertension has a considerable worldwide burden and is a major risk factor for cardiovascular disease. Despite the use of lifestyle measures and medical therapy, a large proportion of patients remain treatment ‘resistant’ and fail to have adequate control of blood pressure. This may adversely affect both future cardiovascular events and mortality. Catheter-based renal denervation is a promising contemporary evolution of a historical treatment for hypertension and aims to achieve a reduction in renal sympathetic activation. This has been shown previously to be important in both resistant hypertension and in other disease states including heart failure. This review will focus on contemporary evidence supporting the utility of renal denervation, review current and emerging devices, consider potential future treatment indications, and discuss unresolved issues that need to be addressed before renal denervation can be embraced as mainstream therapy.

Objectives This study sought to perform clinical and imaging assessments of the DESolve Bioresorbable Coronary Scaffold (BCS). Background BCS, which is drug eluting, may have potential advantages compared with conventional metallic drug-eluting stents. The DESolve system, designed to provide vessel support and neointimal suppression, combines a poly-l-lactic acid–based scaffold with the antiproliferative myolimus. Methods The DESolve First-in-Man (A NON-RANDOMIZED, CONSECUTIVE ENROLLMENT EVALUATION OF THE DESolve MYOLIMUS ELUTING BIORESORBABLE CORONARY STENT IN THE TREATMENT OF PATIENTS WITH DE NOVO NATIVE CORONARY ARTERY LESIONS) trial was a prospective multicenter study enrolling 16 patients eligible for treatment. The principal safety endpoint was a composite of cardiac death, myocardial infarction, and clinically indicated target lesion revascularization. The principal imaging endpoint was in-scaffold late lumen loss (LLL) assessed by quantitative coronary angiography (QCA) at 6 months. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) imaging was performed at baseline and 6 months; multislice computed tomography (MSCT) was performed at 12 months. Results Acute procedural success was achieved in 15 of 15 patients receiving a study scaffold. At 12 months, there was no scaffold thrombosis and no major adverse cardiac events directly attributable to the scaffold. At 6 months, in-scaffold LLL (by QCA) was 0.19 ± 0.19 mm; neointimal volume (by IVUS) was 7.19 ± 3.56%, with no evidence of scaffold recoil or late malapposition. Findings were confirmed with OCT and showed uniform, thin neointimal coverage (0.12 ± 0.04 mm). At 12 months, MSCT demonstrated excellent vessel patency. Conclusions This study demonstrated the feasibility and efficacy of the DESolve BCS. Results showing low in-scaffold LLL, low % neointimal volume at 6 months, no chronic recoil, and maintenance of lumen patency at 12 months prompt further study. (DESolve First-in-Man; EudraCT number 2011-000027-32)

Renal denervation using the point-by-point application of radiofrequency energy delivered by the first-generation Symplicity system is effective in lowering office blood pressure but may be time-consuming. The OneShot Renal Denervation System with a balloon-mounted spiral electrode potentially shortens and simplifies the procedure. This study is a hypothesis-generating first-in-human study to assess feasibility, and to provide preliminary efficacy and safety data.Eligible patients had a baseline office systolic blood pressure ≥160 mmHg (or ≥150 mmHg for diabetics) and were on two or more antihypertensive medications. Nine patients were enrolled. The primary endpoint, the insertion of the OneShot balloon into each renal artery and the delivery of radiofrequency energy, was achieved in 8/9 (89%) of patients. The one failure (the first patient) was due to generator high-impedance safety shut-off threshold set too low for humans. Adverse events were minor. No patient developed renal artery stenosis. Baseline BP was 185.67 ± 18.7 mmHg and the reductions at 1, 3, 6 and 12 months were 30.1 ± 13.6 (p=0.0004), 34.2 ± 20.2 (p=0.002), 33.6 ± 32.2 (p=0.021) and 30.6 ± 22.0 (p=0.019).The OneShot renal denervation system successfully delivered radiofrequency energy to the renal arteries in a short and straightforward procedure. Australian New Zealand Clinical Trials Registry - URL: anzctr.org.au. Trial identification: ACTRN12611000987965.

Percutaneous transcatheter renal sympathetic denervation (RDN) is a promising treatment for refractory hypertension (HT). RDN was found in one series of clinical studies to reduce systolic blood pressure (SBP) by as much as a mean of 30 mmHg with 85% of subjects experiencing sustained reductions of 10 mm or more out to two years after RDN. This degree of blood pressure reduction may reduce stroke and myocardial infarction rates and is anticipated to translate into improved life expectancy. The lowering of blood pressure by RDN has been shown to improve glycaemic control and reverse left ventricular hypertrophy. Beneficial effects on renal function, sleep apnoea and heart failure are suggested as well. This report describes the first patient treated using the OneShot™ Renal Denervation System (formerly Maya Medical now Covidien, Campbell, CA, USA).

Objectives Our aim was to assess whether a higher clopidogrel maintenance dose has a greater antiplatelet effect in CYP2C19*2 allele carriers compared with noncarriers. Background Clopidogrel is a prodrug that is biotransformed by the cytochrome P450 enzymes CYP2C19, 2C9, and 3A4, 2B6, 1A2. The CYPC219*2 loss of function variant has been associated with a reduced antiplatelet response to clopidogrel and a 3-fold risk of stent thrombosis. Methods Forty patients on standard maintenance dosage clopidogrel (75 mg), for 9.4 ± 9.2 weeks, were enrolled into a dose escalation study. Platelet function was assessed at baseline and after 1 week of 150 mg once daily using the VerifyNow platelet function analyzer (Accumetrics Ltd., San Diego, California). Genomic DNA was hybridized to a BioFilmChip microarray on the INFINITI analyzer (AutoGenomics Inc., Carlsbad, California) and analyzed for the CYP19*2, *4, *17, and CYP2C9*2, *3 polymorphisms. Results Platelet inhibition increased over 1 week, mean +8.6 ± 13.5% (p = 0.0003). Carriers of the CYP2C19*2 allele had significantly reduced platelet inhibition at baseline (median 18%, range 0% to 72%) compared with wildtype (wt) (median 59%, range 11% to 95%, p = 0.01) and at 1 week (p = 0.03). CYP2C19*2 allele carriers had an increase in platelet inhibition of (mean +9 ± 11%, p = 0.03) and reduction in platelet reactivity (mean −26 ± 38 platelet response unit, p = 0.04) with a higher dose. Together CYP2C19*2 and CYP2C9*3 loss of function carriers had a greater change in platelet inhibition with 150 mg daily than wt/wt (+10.9% vs. +0.7%, p = 0.04). Conclusions Increasing the dose of clopidogrel in patients with nonresponder polymorphisms can increase antiplatelet response. Personalizing clopidogrel dosing using pharmacogenomics may be an effective method of optimizing treatment.

Objectives The aim of this study was to determine the safety and efficacy of a novel pimecrolimus-eluting stent in a porcine coronary model and in a phase I clinical trial. Background Rapamycin- and paclitaxel-eluting stents reduce the need for repeat intervention by limiting neointimal hyperplasia but might cause delayed healing, pre-disposing patients to late stent thrombosis. Because inflammation plays a key role in restenosis, pimecrolimus, an anti-inflammatory drug, might reduce restenosis without adversely affecting re-endothelialization. Methods We evaluated a novel polymeric pimecrolimus-eluting stent covered with a thin parylene C diffusion barrier in a porcine coronary model and in a phase I human clinical trial. The clinical study was a prospective, nonrandomized, first-in-human hypothesis-generating study that enrolled 15 patients who had a single de novo native coronary stenosis. Results At 28 days and 3 months in the porcine model, histopathologic indicators predicted safety and biocompatibility when stents coated with polymer only, drug only, and 2 drug-polymer formulations were compared with bare-metal stents (BMS). In the phase I clinical trial, 15 patients had successful implantation of pimecrolimus-eluting stents. By 6 months, no patient suffered death, myocardial infarction, or stent thrombosis. However, the angiographic restenosis (61%), mean late loss (1.44 mm), and repeat target lesion revascularization (53%) were significantly higher than historical BMS controls. Whereas the primary end point was percent volume obstruction, restenosis was so severe that operators performed intravascular ultrasound examination in only 6 patients. Conclusions Pimecrolimus-eluting stents induced an exaggerated neointimal hyperplasia at 6 months in comparison with historical controls.

Objectives This study assessed the effect of pharmacogenetics on the antiplatelet effect of clopidogrel. Background Variability in clopidogrel response might be influenced by polymorphisms in genes coding for drug metabolism enzymes (cytochrome P450 [CYP] family), transport proteins (P-glycoprotein) and/or target proteins for the drug (adenosine diphosphate–receptor P2Y12). Methods Sixty patients undergoing elective percutaneous coronary intervention in the randomized PRINC (Plavix Response in Coronary Intervention) trial had platelet function measured using the VerifyNow P2Y12 analyzer after a 600-mg or split 1,200-mg loading dose and after a 75- or 150-mg daily maintenance dosage. Polymerase chain reaction–based genotyping evaluated polymorphisms in the CYP2C19, CYP2C9, CYP3A4, CYP3A5, ABCB1, P2Y12, and CES genes. Results CYP2C19*1*1 carriers had greater platelet inhibition 2 h after a 600-mg dose (median: 23%, range: 0% to 66%), compared with platelet inhibition in CYP2C19*2 or *4 carriers (10%, 0% to 56%, p = 0.029) and CYP2C19*17 carriers (9%, 0% to 98%, p = 0.026). CYP2C19*2 or *4 carriers had greater platelet inhibition with the higher loading dose than with the lower dose at 4 h (37%, 8% to 87% vs. 14%, 0% to 22%, p = 0.002) and responded better with the higher maintenance dose regimen (51%, 15% to 86% vs. 14%, 0% to 67%, p = 0.042). Conclusions Carriers of the CYP2C19*2 and *4 alleles showed reduced platelet inhibition after a clopidogrel 600-mg loading dose but responded to higher loading and maintenance dose regimens. Genotyping for the relevant gene polymorphisms may help to individualize and optimize clopidogrel treatment. (Australia New Zealand Clinical Trials Registry; ACTRN12606000129583)

Objectives This study evaluated the antiplatelet effect of a higher loading and maintenance dose regimen of clopidogrel and a possible drug interaction with verapamil. Background Clopidogrel loading doses above 600 mg have not resulted in more rapid or complete platelet inhibition. Higher maintenance dosages may be more effective than 75 mg/day. Methods A double-blind, randomized, placebo-controlled trial was undertaken in 60 patients undergoing percutaneous coronary intervention. All patients received clopidogrel 600 mg at the start of the procedure. Using a 2 × 2 design, patients were allocated to clopidogrel 600 mg given 2 h later or matching placebo, and to verapamil 5 mg intra-arterial or placebo. Platelet function was measured using the VerifyNow P2Y12 analyzer (Accumetrics Ltd., San Diego, California) at 2, 4, and 7 h. Patients were further randomized to receive a clopidogrel 75 or 150 mg once daily, with platelet function assessed after 1 week. Results Two hours after the second dose of clopidogrel or placebo, platelet inhibition was 42 ± 27% with clopidogrel, compared with 24 ± 22% with placebo (p = 0.0006). By 5 h after the second dose, platelet inhibition was 49 ± 30% with clopidogrel, compared with 29 ± 22% with placebo (p = 0.01). No drug interaction was seen with verapamil. A clopidogrel maintenance dosage of 150 mg daily for 1 week resulted in greater platelet inhibition than 75 mg daily (50 ± 28% vs. 29 ± 19%, p = 0.01). Conclusions In an unselected population undergoing percutaneous coronary intervention a clopidogrel 1,200-mg loading dose, given as two 600-mg doses 2 h apart, results in more rapid and complete platelet inhibition than a single 600-mg dose. A maintenance dosage of 150 mg daily produces greater platelet inhibition than 75 mg daily. (The PRINC trial; ACTRN12606000129583)

Background Coronary angiography is the gold standard for assessing coronary artery disease (CAD). In many patients with chest pain, no or mild CAD (< 50% stenosis) is found. It is uncertain whether this 'non-significant' result influences management and outcomes. We reviewed characteristics and outcomes in a contemporary cohort of chest pain referrals who had mild or absent CAD on coronary angiography. Method All patients undergoing coronary angiography at Auckland City Hospital during July 2010-October 2011 were reviewed (n = 2983). Of these, 12.3% (n = 366) underwent coronary angiography for evaluation of chest pain and were found to have absent or mild CAD. These patients were followed up for 2.3 ± 0.6 years. Results Mean age was 60.0 ± 12.3 years, 56.1% were female. The ECG was abnormal in 55.0% of patients. Stress testing for inducible ischaemia was undertaken in 40.7% of patients and was abnormal in 57.7%. Following angiography, 43.2% had no changes to cardiac medications. Additional drug therapy (aspirin, statin, beta-blockers, ACE-inhibitor) was commenced in around 14.2-22.1% of cases. These drugs were discontinued in 4.1-8.2% of patients. Rates of major adverse cardiovascular events and readmissions with chest pain were 0.3% (1) and 1.9% (7) respectively at 30 days, and 1.9% (7) and 6.0% (22) at 1 year. Conclusion Although even non-obstructive atheroma may justify medical therapy to limit disease progression, our findings may suggest that in these cases, invasive coronary angiography, may not lead to the patient/physician reassurance justified by historical data.

We evaluated the effectiveness of manual pressure hemostasis after transfemoral coronary angiography in patients on therapeutic warfarin anticoagulation (international normalized ratio [INR] 2.0 to 3.0) compared with discontinuing warfarinor =48 hours before the procedure (INR2.0). There was a low incidence of small hematomas with either strategy (no significant difference) and no major vascular complications. No prolonged hospital stay due to an access site complication was observed, and no thromboembolic events occurred. In conclusion, transfemoral coronary angiography appears to be safe in patients on warfarin with an INR of 2.0 to 3.0).

Background— The Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial demonstrated the survival advantage of emergency revascularization versus initial medical stabilization in patients developing cardiogenic shock after acute myocardial infarction. The relative merits of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in patients with shock have not been defined. The objective of this analysis was to compare the effects of PCI and CABG on 30-day and 1-year survival in the SHOCK trial. Methods and Results— Of the 302 trial patients, 128 with predominant left ventricular failure had emergency revascularization. The selection of revascularization procedures was individualized. Eighty-one patients (63.3%) had PCI, and 47 (36.7%) had CABG. The median time from randomization to intervention was 0.9 hours (interquartile range [IQR], 0.3 to 2.2 hours) for PCI and 2.7 hours (IQR, 1.3 to 5.5 hours) for CABG. Baseline demographics and hemodynamics were similar, except that there were more diabetics (48.9% versus 26.9%; P =0.02), 3-vessel disease (80.4% versus 60.3%; P =0.03), and left main coronary disease (41.3% versus 13.0%; P =0.001) in the CABG group. In the PCI group, 12.3% had 2-vessel and 2.5% had 3-vessel interventions. In the CABG group, 84.8% received ≥2 grafts, 52.2% received ≥3 grafts, and 87.2% were deemed completely revascularized. The survival rates were 55.6% in the PCI group compared with 57.4% in the CABG group at 30 days ( P =0.86) and 51.9% compared with 46.8%, respectively, at 1 year ( P =0.71). Conclusions— Among SHOCK trial patients randomized to emergency revascularization, those treated with CABG had a greater prevalence of diabetes and worse coronary disease than those treated with PCI. However, survival rates were similar. Emergency CABG is an important component of an optimal treatment strategy in patients with cardiogenic shock, and should be considered a complementary treatment option in patients with extensive coronary disease.

A fast and sensitive high performance liquid chromatography (HPLC) assay was developed on a C18 monolithic column for the simultaneous determination of acetaminophen-caffeine-butalbital in human serum. Serum samples were treated with a solid phase extraction procedure. The analytes were separated using a mobile phase of 95:5 (v/v) 0.1M potassium phosphate monobasic (pH 2.41)-acetonitrile on the C18 monolithic column with detection at 220 nm. Benzoic acid was used as the internal standard (IS). The method was validated over the range of 1.25-100 microg/ml for each drug and found to be linear (r > 0.995, n = 12) with RSD less than 8.3%. The method proved to be accurate (percent bias for all calibration samples varied from -14.6 to -1.3%) and precise (ranged from 2.9 to 13.4%). The mean percent absolute recoveries from serum were 89.7 +/- 3.6 for acetaminophen, 95.5 +/- 4.5 for caffeine, 99 +/- 5.2 for butalbital and 83.4 +/- 3.9% for the internal standard.

A direct plasma injection HPLC method has been developed for the determination of selected benzodiazepines (nitrazepam, clobazam, oxazepam, lorazepam). The method uses an analytical hydrophobic shielded phase (Hisep) column equipped with a Hisep guard column, are easy to perform and requires 20 ul of a filtered plasma sample. The chromatographic run time is less than 15 min using a mobile phase of 15:85 v/v acetonitrile-0.18 M ammonium acetate pH 2.5. The method is good for 175 injections before replacement of the guard column. The method was linear in the range 0.5-18 ug ml(-1) (r>0.99, n=6) for the analytes with R.S.D. less than 10.82%. Interday and intraday variability were found to be less than 14%. The limits of detection and quantitation were 0.16 (s/n>3) and 0.5 ug ml(-1) (s/n>10), respectively, for each of the four benzodiazepines.

A fast and sensitive high performance liquid chromatography (HPLC) assay was developed for the simultaneous determination of aspirin–butalbital in human serum. Serum samples were treated with a solid phase extraction procedure. The analytes were separated using a mobile phase of 90:10 (v/v) 0.1 M aqueous potassium phosphate monobasic (pH 4)‐acetonitrile on a monolithic C18 column with UV detection at 220 nm. Benzoic acid was used as the internal standard (IS). The method was validated over the range of 0.5–100 µg mL−1 for each drug. The method proved to be accurate (percent bias for all calibration samples varied from −13 to 6.6%) and precise (range from 0.1% to 10%). The mean percent absolute recoveries were 104 ± 6.3 for aspirin, 92.6 ± 5.5 for butalbital and 106 ± 6.9 for the internal standard. The assay should be applicable for use in pharmacokinetic studies and routine serum monitoring of these drugs.

Retrospective analyses of patient cohorts undergoing stent deployment have shown that small vessel diameter and long lesion length are two angiographic predictors of increased restenosis. We determined the effects of these factors in patients with lesions treated in both small- and large-diameter coronary arteries. This multicenter prospective quantitative angiographic study evaluated patients with de novo coronary disease undergoing intervention who had at least two lesionsor = 16 mm length, one in a vesselor = 2.75 mm diameter (9 or 16 mm length seven-cell NIR stent) and the other in a vesselor = 3.0 mm diameter (9 or 16 mm nine-cell NIR stent). Of 94 patients enrolled, 76% were male, mean age was 62 years (range, 40-85), 41% were hypertensive, 18% had diabetes, 15% were current smokers, and 64% had hypercholesterolemia. Additional lesions were treated in 23% of patients. The procedural success rate was 99%. Six months postprocedure, there were no deaths or late stent occlusions. One patient suffered a Q-wave myocardial infarction, one a non-Q-wave infarction, eight underwent percutaneous reintervention, two coronary artery bypass graft surgery operations, and five stenting of other nonstudy lesions. The mean reference diameter for the small vessel was 2.35 mm and the large vessel 3.22 mm. Six-month angiography was performed in 87 patients (92% of those eligible). The overall restenosis rate was 24% in the small vessel (9 mm length stent, 17%; 16 mm length stent, 30%) and 15% in the large vessel (9 mm length stent, 3%; 16 mm length stent, 22%), respectively. Multivessel stenting including treatment of lesions in small-caliber vessels can be performed with a good clinical and angiographic outcome. When the patient, operator, technique, and stent type are the same, vessel caliber and stent length both appear to influence the restenosis rate.

Two new high performance liquid chromatography (HPLC) assays were developed, which utilized a 100 × 4.6 mm I.D. monolithic silica column and binary mobile phase gradients, for the simultaneous determination of selected drugs of abuse in human plasma. Both methods used gradients consisting of 25 mM pentanesulfonic acid and 25 mM sodium phosphate monobasic monohydrate-acetonitrile (pH 2.9), and mixed mode solid phase extraction procedures. In the first method, cocaine (COC) and its metabolites benzoylecgonine (BE), norcocaine (NC), and cocaethylene (CE), were separated with a pump flow rate of 5.0 mL/min in a total run time of 5 min. All analyses were conducted at ambient temperature. The injection volume was 100 µL and the UV detector was operated at 231 nm. The method was validated over the range of 50–5000 ng/mL for BE, COC, and CE, and 25–2500 ng/mL for NC. The method proved to be accurate (% bias for all calibration samples varied from −4.5 to 8.5%) and precise (within-run precision ranged fro...

Micellar electrokinetic chromatography methods were developed and validated to separate and quantitate anti-HIV drug mixtures containing zidovudine(AZT)/didanosine(ddI)/nevirapine (mixture A) and AZT/ddI/ritonavir (mixture B) in human serum. Serum samples were prepared using a solid-phase extraction procedure. The effects of various factors such as buffer type, buffer and surfactant concentrations, and pH on the separations were investigated. The optimized resolution was achieved with a run buffer containing 18 mM sodium dodecylsulfate in 15 mM phosphate and borate buffer (pH 9.0). An uncoated 52 cm (effective length 30 cm)x50 micrometer ID fused-silica capillary operated at 30 degrees C was used in the analysis with UV detection at 210 nm. Aprobarbital was chosen as the internal standard. All analytes were separated within 14 min with a voltage of +15 kV and a current around 30 microA. The methods were validated over the range of 0.5-25.0 microgram/ml for AZT, 0.8-18.5 microgram/ml for ddI, 0.5-22.8 microgram/ml for nevirapine in mixture A and the range of 0.5-25.0 microgram/ml for AZT, 0.8-18.5 microgram/ml for ddI, 1.2-28.8 microgram/ml for ritonavir in mixture B. Intra-day and inter-day accuracy was less than 12.4% and intra-day and inter-day precision was less than 13.9% for both mixtures. Extraction recoveries of all analytes from serum were higher than 75.9%. The assay should be applicable to pharmacokinetic studies and routine monitoring of these drugs in serum.

Moxifloxacin is an advanced-generation, 8-methoxy fluoroquinolone that is active against a broad spectrum of pathogens, including antibiotic resistant Streptococcus pneumoniae. Development of a rapid, sensitive and selective method for the determination of moxifloxacin in human plasma is essential for understanding the pharmacokinetics of the drug when administered orally or intravenously. Solid phase extraction (SPE) using Oasis® HLB was used to extract moxifloxacin and the internal standard lomefloxacin from plasma. A method based on liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI–MS/MS) was developed and validated to quantitate moxifloxacin in human plasma. The precursor and major product ion of the analyte was monitored on a triple quadrupole mass spectrometer with positive ion electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. Mechanisms for the formation of collision-induced dissociation (CID) products of moxifloxacin are proposed. Linear calibration curves were generated from 1 to 1000 ng/ml with coefficients of determination greater than 0.999. The inter-day and intra-day precision (% CV) was less than 11.3% and accuracy (% error) was less than 10.0% for moxifloxacin. The limit of detection (LOD) for the method was 50 pg/ml based on a signal to noise ratio of 3.

A high-performance liquid chromatography method has been developed and validated for the simultaneous determination of amoxicillin, metronidazole, and pantoprazole in human plasma. Solid-phase extr...

An enantioseparation of racemic vesamicol in human serum by capillary electrophoresis with solid phase extraction and sulfated B-cyclodextrin (S-B-CD) is presented The separation was achieved on an uncoated 72 cm x 50 microm id fused silica capillary maintained at 30 degrees C and + 15 kV applied voltage using a run buffer of 128 micro-B-CD in 50 mM phosphate buffer at pH 5. The detection wavelength was 260 nm. Bond Elut C18 solid phase extraction cartridges were used in the sample preparation of the vesamicol samples from serum. Among the CDs studied, the migration order of the enantiomers was reversed in CM-B-CD compared to S-B-CD. Increases in migration time and differences in time between enantiomers was observed with increasing concentrations of S-B-CD. Baseline separation was achieved in the 2-20 microg/ml range of enantiomer concentration (r.996). A sample stacking technique was used to improve peak shape and LOD. LODs were 0.5 microg/ml for each enantiomer. Studies of various factors and CE conditions showed the effect of CD type, CD concentration, buffer type, buffer concentration and pH on stability and resolution.

A new high performance liquid chromatography (HPLC) assay was developed for the simultaneous determination of zidovudine (AZT) and levofloxacin in human plasma. Plasma samples were treated with a solid-phase extraction procedure. The compounds were separated using a mobile phase of 86 : 14 v/v 25 mM sodium phosphate monobasic monohydrate and 0.1% trifluoroacetic acid (pH 2.4) – acetonitrile on an octadecylsilane column (150 × 4.6 mm i.d.) with UV detection at 266 nm. Ciprofloxacin was used as the internal standard (IS). The method was validated over the range of 26.3–2600 ng/mL for AZT, and 51.2–5069 ng/mL for levofloxacin. The method proved to be accurate (percent bias for all calibration samples varied from −6.2 to 5.6%) and precise (within-run precision ranged from 0.9 to 9.7% and between-run precision ranged from 1.3 to 7.5%). The mean absolute recoveries were 94.1% for AZT, 91.2% for levofloxacin, and 84.7% for the internal standard. The assay should be suitable for use in pharmacokinetic st...

Stability-indicating, reversed phase high-performance liquid chromatographic (HPLC) methods have been developed for the determination of several procaine hydrochloride and prilocaine hydrochloride combinations. The separation and quantitation of epinephrine-prilocaine and epinephrine-procaine drug combinations were achieved on a phenyl column using a mobile phase of 80:20% v/v 25 mM phosphate buffer (pH 3.0) containing 50 mM heptanesulfonic acid sodium salt-acetonitrile at a flow rate of 1 ml x min(-1) and UV detection at 254 nm. The method showed linearity for the epinephrine and prilocaine hydrochloride mixture in the 0.25-2.5 and 8-200 micro g ml(-1) ranges, respectively. The intra- and inter-day relative standard deviations (RSDs) ranged from 0.26 to 2.05% and 0.04 to 0.61% for epinephrine and prilocaine hydrochloride, respectively. The epinephrine and procaine hydrochloride mixture yielded linear ranges of 0.25-2.0 and 5-100 micro g ml(-1) and intra- and inter-day RSDs ranged from 0.23 to 1.88% and 0.07 to 0.26% for epinephrine and procaine hydrochloride, respectively. The assays were shown to be suitable for measuring epinephrine-prilocaine and epinephrine-procaine combinations in their respective injection dosage forms. Stability-indicating HPLC assays were also developed for several other procaine drug combinations since their monographs are present in the USP 24; however, quantitation was not investigated since these combinations are not commercially available. A mobile phase consisting of 80:20% v/v 25 mM phosphate buffer (pH 3.0) containing 50 mM heptanesulfonic acid-acetonitrile was utilized for the levonordefrin-tetracaine-procaine drug combination, while a mobile phase consisting of 70:30% v/v 25 mM phosphate buffer (pH 3.0) containing 50 mM heptanesulfonic acid sodium salt-acetonitrile was utilized for the separation of levonordefrin-procaine-propoxycaine and norepinephrine-procaine-propoxycaine. All separations were achieved on a phenyl column at a flow rate of 1 ml x min(-1) and UV detection at 254 nm.

A new high-performance liquid chromatography (HPLC) assay was developed for the simultaneous determination of zidovudine (AZT)/lamivudine (3TC)/nevirapine in human plasma. Plasma samples were treated using a solid-phase extraction procedure. The compounds were separated using a mobile phase of 20 mM sodium phosphate buffer (containing 8 mM 1-octanesulfonic acid sodium salt)–acetonitrile (86:14, v/v) with pH adjusted to 3.2 with phosphoric acid on an octylsilane column (150×3.9 mm i.d.) with UV detection at 265 nm. Aprobarbital was chosen as the internal standard (IS). The method was validated over the range of 57.6–2880 ng/ml for AZT, 59.0–17 650 ng/ml for 3TC and 53.2–13 300 ng/ml for nevirapine. The method was shown to be accurate, with intra-day and inter-day accuracy from 0.1 to 11% and precise, with intra-day and inter-day precision from 0.4 to 14%. Extraction recoveries of the analytes and IS from plasma were higher than 92%. The assay should be suitable for use in pharmacokinetic studies and routine plasma monitoring of this triple-drug therapy in AIDS patients.

Anti-HIV drug mixtures A and B containing stavudine(d4T)/didanosine (ddI)/saquinavir and stavudine (d4T)/didanosine (ddI)/efavirenz, respectively, were separated and quantitated in human serum using micellar electrokinetic chromatography (MEKC). Serum samples were treated using a solid-phase extraction procedure. The effects of various factors such as buffer type, buffer and surfactant concentration, and pH on the separation of the analytes were investigated. The optimized resolution of both mixtures was achieved with a run buffer containing 18 mM sodium dodecylsulfate (SDS) in 15 mM phosphate and borate buffer (pH 9.0). An uncoated 52 cm (effective length 30 cm) × 50 μm ID fused-silica capillary, operated at 30°C, was used in the analysis with UV detection at 210 nm. Aprobarbital was chosen as the internal standard. All analytes were separated within 15 min with a voltage of +15 kV and a current around 30 μA. The methods were validated over the range of 0.7–35.3 μg/mL for d4T, 0.8–18.5 μg/mL for ddI...

The anti-HIV drug mixture of lamivudine (3TC), didanosine (ddI), and saquinavir was separated and quantitated in human serum with capillary zone electrophoresis. Serum samples were treated using a solid-phase extraction procedure. The effects of various factors, such as run buffer type, buffer concentration, and pH on the separation were investigated. The optimized resolution was achieved with a run buffer containing 100 nM N,N-dimethyloctylamine in 80 mM phosphate buffer (pH 2.5). An uncoated 52 cm (effective length 30 cm) × 50 μm ID fused-silica capillary operated at 30°C was used in the analysis with UV detection at 210 nm. Diltiazem was chosen as an internal standard. All analytes were separated within 10 min with a voltage of + 20 kV and a current around 30 μA. The method was validated over the range of 0.4–37.8 μg/mL for 3TC, 1.4–34 μg/mL for ddI and 0.5–24.4 μg/mL for saquinavir. Intra-day and inter-day accuracy was less than 13.7% and intra-day and inter-day precision was less than 13.3%. Extracti...

Aims Primary percutaneous coronary intervention (PCI) is the optimal management for ST segment elevation myocardial infarction (STEMI) patients. We reviewed the largest primary PCI regional service in New Zealand: the Auckland/Northland service based at Auckland City Hospital, to assess patient management, in particular the door to reperfusion times (DTRTs), and predictors of death in hospital. Methods We obtained patient details from a comprehensive prospective database of all primary PCI patients admitted with STEMI from 1/1/12 to 31/12/12 to the Auckland City Hospital cardiac catheterisation laboratory. Of four District Health Boards (DHBs) within the region, two accessed this regional service at all times, and two accessed the Auckland City Hospital cardiac catheterisation laboratory ‘after hours’: all times except for 08:00 to 16:00 hours on Monday to Friday. Results A total of 401 adult patients underwent a primary PCI at the Auckland City Hospital Regional centre for a STEMI presentation, over the 12 months period. The median patient age was 61 years, 77% were male. Overall 183 (46%) (95% CI 41, 51) patients achieved a DTRT of 90 mins, and 266 (66%) (95% CI 61, 71) a DTRT of 120mins, with a clear geographical influence to these times. Of 27 patients with direct transfer to the catheter laboratory from the community, the DTRT was 120 mins in 24 (92%) (95% CI 72, 96) patients. In-hospital mortality was 24 (6%) patients (95% CI 4, 9). Conclusions The 2012 Auckland/Northland primary PCI service delivers good outcomes consistent with current Australasian standards. Although geographical isolation complicates door to reperfusion times, these may potentially be improved by more focus on direct transfer to the cardiac catheterisation laboratory, especially directly from the community.

A novel high-performance liquid chromatography (HPLC) assay was developed for the simultaneous determination of zidovudine (AZT)/zalcitabine (ddC)/nevirapine in human plasma. Plasma samples were treated using a solid-phase extraction procedure. The analytes were separated using a mobile phase containing 20 mM sodium phosphate buffer (containing 8 mM 1-octanesulfonic acid, sodium salt)-acetonitrile (86:14, v/v) with pH adjusted to 3.2 with phosphoric acid on an octylsilane column (150 × 3.9 mm I.D.) with UV detection at 265 nm. Aprobarbital was chosen as internal standard. The method was validated over the range of 57.6–2880 ng/mL for AZT, 20.2–2020 ng/mL for ddC and 53.2–13300 ng/mL for nevirapine. Intra-day and inter-day accuracy were less than 10.7% and intra-day and inter-day precision were less than 13.7%. Extraction recoveries of all analytes from plasma were higher than 88.5%. The assay should be applicable for pharmacokinetic studies and routine monitoring of these drugs in plasma.

Acid, base, heat, oxidation and UV irradiation stress methods were applied to study the stability of the bulk drug form of sumatriptan succinate. Liquid chromatography coupled with mass spectrometry (LC-MS and LC-MS-MS) was used to analyze the degraded samples and tentative structural identifications were assigned based upon known reactivity of the drug, molecular weight measurements and MS-MS fragmentation patterns. Sumatriptan succinate was found to be stable to exposure of acid, base, oxidation and UV irradiation at ambient conditions, but was found to degrade under acidic, basic and oxidative conditions when heated to 90 degrees C.

Gatifloxacin is an advanced-generation, 8-methoxyfluoroquinolone that is active against a broad spectrum of pathogens, including antiobiotic resistant Streptococcus pneumoniae. Development of a rapid, sensitive and selective method for the determination of gatifloxacin in human plasma is essential for understanding the pharmacokinetics of the drug when administered orally or intravenously. Solid phase extraction (SPE) using Oasis HLB was used to extract gatifloxacin and the internal standard ciprofloxacin from plasma. A method based on liquid chromatography/electrospray tandem mass spectrometry (LC/ESI-MS/MS) was developed and validated to quantitate gatifloxacin in human plasma. The precursor and major product ions of the analyte were monitored on a triple quadrupole mass spectrometer with positive ion electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. Mechanisms for the formation of collision-induced dissociation products of gatifloxacin are proposed. Linear calibration curves were generated from 10--1000 ng/mL with coefficients of determination greater than 0.99. The interday and intraday precision (%RSD) was less than 6.0% and accuracy (%error) was less than 5.4% for gatifloxacin. The limit of detection (LOD) for the method was 500 pg/mL based on a signal-to-noise ratio of 3.

Nitric oxide (NO) is synthesized from L-arginine (ARG) catalyzed by the enzyme nitric oxide synthase (NOS) and is important in the regulation of vascular tone, neurotransmission and host defense. N,N-Dimethyl L-arginine (asymmetric dimethylarginine, ADMA) and N-monomethyl L-arginine (MMA) are endogenous inhibitors of NOS. N,N'-Dimethyl L-arginine (symmetric dimethylarginine, SDMA), the inactive enantiomer of ADMA is also known to be present endogenously. A simple, sensitive and fast LC-MS-MS method was developed to extract and quantitate ADMA, SDMA, MMA and ARG from human plasma. 13C6-ARG was used as the internal standard for the assay. Protein precipitation using acetonitrile gave good recoveries of all the compounds from plasma. The compounds were separated by HPLC in less than 15 min using a silica column. The limits of detection for this method were found to be approximately 1 ng/ml for ARG, ADMA and SDMA and 2.5 ng/ml for MMA. The total LC-MS-MS analysis time is less than 15 min making this the fastest and most specific method reported to date. The use of an isocratic liquid chromatographic separation makes this method optimal for high sample throughput. The inter- and intra-day precision (% RSD) and accuracy (% error) for this assay were less than 15%. The average concentrations of ARG, ADMA, SDMA and MMA in plasma from 20 human subjects were found to be 10.9+/-4.1 microg/ml, 25.1+/-9.4 ng/ml, 33.2+/-13.1 ng/ml and 19.6+/-3.8 ng/ml, respectively.

Cefepime hydrochloride injection 2 g (Maxipime) was mixed with metronidazole injection USP (Flagyl IV ready-to-use, 500 mg/100 mL) and metronidazole hydrochloride IV (Flagyl HCI IV, 500 mg) reconstituted with 0.9% sodium chloride injection USP and/or 5% dextrose injection USP to yield cefepime concentrations of 2, 1, 0.5, and 0.25 g and 500 mg metronidazole per 100 mL of solution. The mixtures were stored in polyvinyl chloride bags up to 168 hours at 4°C and at 22°–24°C. Cefepime and metronidazole mixtures in metronidazole injection USP were stable up to 168 hours and 96–168 hours, respectively, stored in PVC bags at 4°C. The 2.5 mg/mL cefepime and 5.0 mg/mL metronidazole mixtures were stable up to 8 and 72 hours, respectively. Identical mixtures stored at 22°–24°C were stable up to 8–48 and 12–24 hours for cefepime and metronidazole, respectively. Cefepime and metronidazole mixtures in metronidazole HCl IV reconstituted with 0.9% sodium chloride injection USP were stable for 24–168 hours, respectively, stored in PVC bags at 4°C. Identical mixtures of cefepime and metronidazole stored at 22°–24°C were stable for 8–24 and 24–168 hours, respectively. Cefepime and metronidazole mixtures in metronidazole HCl IV reconstituted with 5% dextrose injection USP were stable for 8–48 and 81–68 hours, respectively, stored in PVC bags at 4°C. Identical mixtures of cefepime and metronidazole at 22°–24°C were stable for 8–12 and 168 hours, respectively. In general, cefepime and metronidazole controls were more stable than the mixtures.

A high performance liquid chromatography procedure has been developed for the simultaneous determination of guaifenesin pseudoephedrine-dextromethorphan and guaifenesin-pseudoephedrine in commercially available capsule dosage forms and guaifenesin-codeine in a commercial cough syrup dosage form. The separation and quantitation are achieved on a 25-cm underivatized silica column using a mobile phase of 60:40%) v/v 6.25 mM phosphate buffer, pH 3.0 - acetonitrile at a flow rate of 1 ml min(-1) with detection of all analytes at 216 nm. The separation is achieved within 10 min for each drug mixture. The method showed linearity for the guaifenesin-pseudoephedrine-dextromethorphan mixture in the 50-200, 7.5-30 and 2.5-10, microg ml(-1) ranges, respectively. The intra- and inter-day RSDs ranged from 0.23 to 4.20%, 0.18 to 2.85%, and 0.13 to 5.04% for guaifenesin, pseudoephedrine, and dextromethorphan, respectively. The guaifenesin pseudoephedrine mixture yielded linear ranges of 25-100 and 3.75-15 microg ml(-1) and intra- and inter-day RSDs ranged from 0.65 to 4.18% and 0.23 to 3.00% for guaifenesin and pseudoephedrine, respectively. The method showed linearity for the guaifenesin-codeine mixture in the 25-100 and 2.5-10 microg ml(-1) ranges and RSDs ranged from 0.37 to 4.25% and 0.14 to 2.08% for guaifenesin and codeine, respectively.