Keith D. Dawkins

Chronic Arterial Responses to Polymer-Controlled Paclitaxel-Eluting Stents Comparison With Bare Metal Stents by Serial Intravascular Ultrasound Analyses: Data From the Randomized TAXUS-II Trial

Background—Polymer-controlled paclitaxel-eluting stents have shown a pronounced reduction in neointimal hyperplasia compared with bare metal stents (BMS). The aim of this substudy was to evaluate local arterial responses through the use of serial quantitative intravascular ultrasound (IVUS) analyses in the TAXUS II trial. Methods and Results—TAXUS II was a randomized, double-blind study with 536 patients in 2 consecutive cohorts comparing slow-release (SR; 131 patients) and moderate-release (MR; 135 patients) paclitaxel-eluting stents with BMS (270 patients). This IVUS substudy included patients treated with one study stent who underwent serial IVUS examination after the procedure and at 6-month follow-up (BMS, 152 patients; SR, 81; MR, 81). The analyzed stented segment (15 mm) was divided into 5 subsegments in which mean vessel area (VA), stent area (SA), lumen area (LA), intrastent neointimal hyperplasia area (NIHA), and peristent area (VA−SA) were measured. NIHA was significantly reduced in SR (0.7±0.9 mm2, P <0.001) and MR (0.6±0.8 mm2, P <0.001) compared with BMS (1.9±1.5 mm2), with no differences between the two paclitaxel-eluting release formulations. Longitudinal distribution of neointimal hyperplasia throughout the paclitaxel-eluting stent was uniform. Neointimal growth was independent of peristent area at postprocedure examination in all groups. There were progressive increases in peristent area from BMS to SR to MR (0.5±1.7, 1.0±1.8, and 1.4±2.0 mm2, respectively; P <0.001). The increase in peristent area was directly correlated with increases in VA. Conclusions—Both SR and MR paclitaxel-eluting stents prevent neointimal formation to the same degree compared with BMS. However, the difference in peristent remodeling suggests a release-dependent effect between SR and MR.

Circulating chlamydia pneumoniaeDNA as a predictor of coronary artery disease

OBJECTIVE To determine whether current vascular Chlamydia pneumoniae (CPn) infection as diagnosed by circulating CPn DNA is more common in subjects with coronary artery disease (CAD). BACKGROUND Serological, pathological and animal studies have associated CPn with CAD and preliminary trials suggest antibiotics may prevent adverse coronary events. C. pneumoniae is thought to disseminate systemically within macrophages. We therefore detected CPn DNA in blood to determine whether its presence was a predictor of CAD. METHODS One thousand, two hundred and five subjects attending for diagnostic and interventional coronary arteriography were recruited. The mononuclear cell layer and platelets were separated from collected blood and the polymerase chain reaction (PCR) was used to detect CPn DNA. RESULTS Circulating CPn DNA was found in 8.8% of 669 men with CAD compared with 2.9% of 135 men with normal coronary arteries (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.1-8.9). In men with CAD, those with CPn DNA had higher mean platelet counts than those without CPn DNA. Monocyte counts and indirect fibrinogen levels were also raised but not significantly so. By contrast, no association of circulating CPn DNA and CAD was seen in women. CONCLUSIONS Circulating CPn DNA is a predictor of CAD in men. Unlike serology, it is a specific indicator of current infection and is a means of identifying subjects who may potentially benefit from antichlamydial therapy.

Direct stenting with TAXUS stents seems to be as safe and effective as with predilatation: A post hoc analysis of TAXUS II

Background and Method:Although direct coronary stenting does not improve angiographic outcome, it makes sense by reducing procedure times, radiation exposure and costs. Other potential advantages of direct stenting may be a reduction of myocardial ischemia time, which could be clinically relevant in high-risk patients. With the introduction of drug-eluting stents, however, concern arose that direct stenting would possibly damage the polymer coating and change or diminish the efficacy of the programmed drug release. Also, concerns about safety by preventing optimal apposition of single stent struts developed. It is the purpose of this paper to retrospectively analyze the data from the TAXUS-II Trial (536 patients) regarding patients with and without direct stenting. While predilatation was recommended per protocol, direct stenting was not forbidden: thus, direct stenting was performed in 49 patients (TAXUS n = 23, control n = 26).Results:In the TAXUS groups, there was no significant difference regarding major adverse cardiac events (MACE; 7.5% vs. 4.3%), angiographic restenosis in the analysis segment (4.8% vs. 4.3%), late loss (0.28 ± 0.36 vs. 0.33 ± 0.30 mm) or intravas- cular ultrasound-(IVUS-)measured volume obstruction (7.95 ± 9.84% vs. 5.61 ± 7.91%) at six months between the predilated and directly stented patients. The same was true for the patients receiving the control stent. Compared with the directly stented control group, the statistically significant positive effects of TAXUS direct stenting were maintained, regarding angiographic restenosis in the analysis segment (4.3% vs. 30.8%), late loss (0.33 ± 0.30 vs. 0.80 ± 0.62 mm) or IVUS-measured volume obstruction (5.61 ± 7.91% vs. 22.50 ± 21.62%) at six months. MACE was reduced from 19.2% to 4.3%; due to the small number of patients this trend did not reach statistical significance. After predilatation, all parameters were significantly improved by the TAXUS stent.Conclusion:Comparison of patients receiving TAXUS stents with or without predilatation revealed no differences in clinical, angiographic or IVUS parameters at six months. This suggests that direct stenting with the polymer-based paclitaxeleluting TAXUS stent is feasible, safe and equally effective. Randomized trials comparing stenting after predilatation versus direct stenting with drug-eluting stents are warranted.Hintergrund und Methodik:Obwohl das koronare Direkt-Stenting das angiographische Kurz- und Langzeitergebnis nicht verbessert, macht es dennoch Sinn, da es die Prozedurzeiten, Strahlenexposition und die Kosten reduzieren kann. Andere mögliche Vorteile des Direkt-Stentings liegen in einer Reduktion der myokardialen Ischämiezeit, was bei Hochrisikopatienten klinisch relevant sein könnte. Mit der Einführung der Medikamente freisetzenden Stents kamen jedoch Bedenken auf, dass ein Direkt-Stenting möglicherweise die Polymerbeschichtung beschädigen könnte und somit die Wirksamkeit vermindert. Auch eine eventuelle Beeinträchtigung der Sicherheit und Wirksamkeit durch Malapposition einzelner Stentstreben wurde diskutiert. Ziel dieser Arbeit ist es, die Daten der TAXUS-II Studie (536 Patienten) hinsichtlich des Direkt-Stentings retrospektiv zu analysieren. In dieser Studie war die Vordehnung zwar empfohlen, ein Direkt-Stenting aber nicht unerlaubt. Insgesamt wurde ein Direkt-Stenting bei 49 Patienten (23 in der TAXUS-Gruppe, 26 in der Kontrollgruppe) durchgeführt.Ergebnisse:In der TAXUS-Gruppe war nach 6 Monaten zwischen den prädilatierten und den direkt-gestenteten Patienten kein signifikanter Unterschied hinsichtlich MACE (7,5 % vs. 4,3 %), angiographischer Restenose im analysierten Gesamtsegment (4,8 % vs. 4,3 %), late loss (0,28 ± 36 mm vs. 0,33 ± 30 mm) und in der IVUS-gemessenen prozentualen Obstruktion des Stentvolumens (7,95 ± 9,84 vs. 5,61 ± 7,91) erkennbar. Dasselbe galt auch für die Patienten, die einen unbeschichteten Kontrollstent erhielten. Im Vergleich zur direkt gestenteten Kontrollgruppe waren die statistisch signifikanten positiven Effekte des TAXUS-Direkt-Stentings unverändert erhalten: angiographische Restenose im gesamten analysierten Segment (4,3 % vs. 30,8 %), late loss (0,33 ± 0,30 vs. 0,80 ± 0,62 mm) und IVUS-gemessene Volumenobstruktion (5,61 ± 7,91% vs. 22,50 ± 21,62%). MACE wurde von 19,2 % auf 4,3 % reduziert, allerdings erreichte dieser eindeutige Trend aufgrund der kleinen Patientenzahl keine statistische Signifikanz. Nach Vordehnung waren in der TAXUS-Gruppe alle Parameter signifikant besser als in der Kontrollgruppe.Schlussfolgerung:Der Vergleich von Patienten, die einen TAXUS-Stent mit oder ohne Vordehnung erhielten, ließ keinen Unterschied in den klinischen, angiographischen oder IVUSParametern nach 6-Monaten erkennen. Die Ergebnisse zeigen, dass das Direkt-Stenting mit dem Polymer-basierten, Paclitaxel-freisetzenden TAXUS-Stent gut durchführbar, sicher und genauso wirksam ist wie nach Vordehnung. Randomisierte Studien zum Vergleich des Direkt-Stentings mit Stenting nach Vordehnung für Medikamente freisetzende Stents sind wichtig.

Direct Stenting with TAXUS Stents Seems to be as Safe and Effective as with Predilatation

Background and Method:Although direct coronary stenting does not improve angiographic outcome, it makes sense by reducing procedure times, radiation exposure and costs. Other potential advantages of direct stenting may be a reduction of myocardial ischemia time, which could be clinically relevant in high-risk patients. With the introduction of drug-eluting stents, however, concern arose that direct stenting would possibly damage the polymer coating and change or diminish the efficacy of the programmed drug release. Also, concerns about safety by preventing optimal apposition of single stent struts developed. It is the purpose of this paper to retrospectively analyze the data from the TAXUS-II Trial (536 patients) regarding patients with and without direct stenting. While predilatation was recommended per protocol, direct stenting was not forbidden: thus, direct stenting was performed in 49 patients (TAXUS n = 23, control n = 26).Results:In the TAXUS groups, there was no significant difference regarding major adverse cardiac events (MACE; 7.5% vs. 4.3%), angiographic restenosis in the analysis segment (4.8% vs. 4.3%), late loss (0.28 ± 0.36 vs. 0.33 ± 0.30 mm) or intravas- cular ultrasound-(IVUS-)measured volume obstruction (7.95 ± 9.84% vs. 5.61 ± 7.91%) at six months between the predilated and directly stented patients. The same was true for the patients receiving the control stent. Compared with the directly stented control group, the statistically significant positive effects of TAXUS direct stenting were maintained, regarding angiographic restenosis in the analysis segment (4.3% vs. 30.8%), late loss (0.33 ± 0.30 vs. 0.80 ± 0.62 mm) or IVUS-measured volume obstruction (5.61 ± 7.91% vs. 22.50 ± 21.62%) at six months. MACE was reduced from 19.2% to 4.3%; due to the small number of patients this trend did not reach statistical significance. After predilatation, all parameters were significantly improved by the TAXUS stent.Conclusion:Comparison of patients receiving TAXUS stents with or without predilatation revealed no differences in clinical, angiographic or IVUS parameters at six months. This suggests that direct stenting with the polymer-based paclitaxeleluting TAXUS stent is feasible, safe and equally effective. Randomized trials comparing stenting after predilatation versus direct stenting with drug-eluting stents are warranted.Hintergrund und Methodik:Obwohl das koronare Direkt-Stenting das angiographische Kurz- und Langzeitergebnis nicht verbessert, macht es dennoch Sinn, da es die Prozedurzeiten, Strahlenexposition und die Kosten reduzieren kann. Andere mögliche Vorteile des Direkt-Stentings liegen in einer Reduktion der myokardialen Ischämiezeit, was bei Hochrisikopatienten klinisch relevant sein könnte. Mit der Einführung der Medikamente freisetzenden Stents kamen jedoch Bedenken auf, dass ein Direkt-Stenting möglicherweise die Polymerbeschichtung beschädigen könnte und somit die Wirksamkeit vermindert. Auch eine eventuelle Beeinträchtigung der Sicherheit und Wirksamkeit durch Malapposition einzelner Stentstreben wurde diskutiert. Ziel dieser Arbeit ist es, die Daten der TAXUS-II Studie (536 Patienten) hinsichtlich des Direkt-Stentings retrospektiv zu analysieren. In dieser Studie war die Vordehnung zwar empfohlen, ein Direkt-Stenting aber nicht unerlaubt. Insgesamt wurde ein Direkt-Stenting bei 49 Patienten (23 in der TAXUS-Gruppe, 26 in der Kontrollgruppe) durchgeführt.Ergebnisse:In der TAXUS-Gruppe war nach 6 Monaten zwischen den prädilatierten und den direkt-gestenteten Patienten kein signifikanter Unterschied hinsichtlich MACE (7,5 % vs. 4,3 %), angiographischer Restenose im analysierten Gesamtsegment (4,8 % vs. 4,3 %), late loss (0,28 ± 36 mm vs. 0,33 ± 30 mm) und in der IVUS-gemessenen prozentualen Obstruktion des Stentvolumens (7,95 ± 9,84 vs. 5,61 ± 7,91) erkennbar. Dasselbe galt auch für die Patienten, die einen unbeschichteten Kontrollstent erhielten. Im Vergleich zur direkt gestenteten Kontrollgruppe waren die statistisch signifikanten positiven Effekte des TAXUS-Direkt-Stentings unverändert erhalten: angiographische Restenose im gesamten analysierten Segment (4,3 % vs. 30,8 %), late loss (0,33 ± 0,30 vs. 0,80 ± 0,62 mm) und IVUS-gemessene Volumenobstruktion (5,61 ± 7,91% vs. 22,50 ± 21,62%). MACE wurde von 19,2 % auf 4,3 % reduziert, allerdings erreichte dieser eindeutige Trend aufgrund der kleinen Patientenzahl keine statistische Signifikanz. Nach Vordehnung waren in der TAXUS-Gruppe alle Parameter signifikant besser als in der Kontrollgruppe.Schlussfolgerung:Der Vergleich von Patienten, die einen TAXUS-Stent mit oder ohne Vordehnung erhielten, ließ keinen Unterschied in den klinischen, angiographischen oder IVUSParametern nach 6-Monaten erkennen. Die Ergebnisse zeigen, dass das Direkt-Stenting mit dem Polymer-basierten, Paclitaxel-freisetzenden TAXUS-Stent gut durchführbar, sicher und genauso wirksam ist wie nach Vordehnung. Randomisierte Studien zum Vergleich des Direkt-Stentings mit Stenting nach Vordehnung für Medikamente freisetzende Stents sind wichtig.

The NUGGET study: NIR ultra gold-gilded equivalency trial.

This study should clarify whether the gold‐coated NIROYAL stent is equivalent to the stainless steel NIR stent. Patients were randomized to either NIR stent (n = 298) or a NIROYAL stent (n = 305). The primary endpoint was the minimum lumen diameter of the target lesion at 6 months postprocedure. Secondary endpoints focused on clinical events. At 30 days, adverse events were similar in both groups. At 6 months, the minimal lumen diameter was 1.83/1.64 mm (P < 0.001; 95% CI = 0.08–0.30) and the angiographic restenosis rate was 20.6%/37.7% (P < 0.001; 95% CI = −24.7 to −9.3) for NIR/NIROYAL. The 6‐month MACE rates were NIR 7.4% and NIROYAL 10.5% (95% CI = −7.7 to 1.4). Compared to stainless steel stent, the NIROYAL stent demonstrated a smaller minimal lumen diameter, a higher late loss (i.e., higher neointimal hyperplasia in spite of a significantly better initial gain), with higher restenosis and similar MACE rates at 6 months. Catheter Cardiovasc Interv 2004;62:18–25.

Normal right ventricular systolic and diastolic function assessed by krypton-81m equilibrium ventriculography

Krypton-81m equilibrium ventriculography was used to study right ventricular function in 23 healthy male volunteers. Technetium-99m lung perfusion scintigraphy was employed to subtract radionuclide activity within lung during image analysis thereby enhancing image quality. The imaging technique was used to generate a time-activity curve for the right ventricle allowing the definition of indices of normal systolic and diastolic function for the right ventricle. At rest, indices of systolic ejection and diastolic filling were comparable to those previously reported for the left ventricle. Using this imaging technique, movement artifact during exercise reduces image quality and limits accurate measurement of these indices to resting studies.

Uterine artery embolisation for massive uterine fibroids in the presence of submassive pulmonary emboli

A 46-year-old woman was admitted to our hospital with acute shortness of breath and pre-syncope. She had known massive uterine fibroids with a history of menorrhagia and dysmenorrhoea, and had been awaiting total abdominal hysterectomy and bilateral salpingo-oophorectomy. She had no past or family history of venous thromboembolism (VTE). She was an ex-smoker with a 16-pack/year smoking history. On examination, she looked unwell, was sweaty and clammy, but apyrexial. Her heart rate was 130 per minute and her blood pressure was 140/95 mmHg. She was tachypnoeic with a respiratory rate of 28 breaths per minute; however, her chest was clear. Abdominal examination revealed an enormous uterus, equivalent to the size of a 30-week pregnancy. There was no clinical evidence of deep vein thrombosis (DVT). She was hypoxic: oxygen saturation on air was 88%; arterial blood gas measurement on 100% oxygen—pH 7.4, PO2 29.0mmHg, PCO2 3.5mmHg, bicarbonate 18.5mmol/L, base excess of 7.5 mol/L. Her full blood count revealed a microcytic anaemia with a mean cellular volume of 67.9 fl (normal: 81–99 fl) and haemoglobin of 9.4 g/dL (normal: 12.0–15.0 g/L). Her D-dimer was significantly elevated at 1.7 Ag/mL (normal: <0.5 Ag/mL). Other blood tests including renal profile, liver function, thyroid function, C-reactive protein and clotting profile were all within normal limits. Her 12 lead electrocardiogram demonstrated sinus rhythm with right bundle branch block and T wave inversion in V1-3 with classic ‘S1QIIITIII’ changes. Her Chest X-ray showed blunting of the basal pulmonary arteries particularly on the right. Transthoracic echocardiography findings were consistent with submassive pulmonary embolism: the left ventricular size and function was normal; the right ventricle was dilated with moderately impaired systolic function; the right atrium was also dilated; the inferior vena cava was distended and failed to collapsewith inspiration; the estimated right ventricular systolic pressure was 50 mmHg. A contrast CT pulmonary angiogram revealed occlusive thrombus in the proximal basal left and mid and basal right pulmonary arteries. She was initially managed with aggressive fluid resuscitation and was commenced on intravenous unfractionated heparin (target APTT ratio of 2.0–3.0). On day 3 she began to heavily menstruate and required a total of nine units of blood over the ensuing 10 days. She was given subcutaneous Zoladex and 30 mg TDS provera to reduce her menstrual blood loss. On day 13 she underwent iliac venography and inferior cavography with insertion of a temporary IVC filter. No free intravascular thrombus was seen in either common iliac vein or within the IVC. There was however significant compression on all three of these veins. Immediately following this, she underwent uterine artery embolisation (UAE). At the time of UAE, her uterus and dominant fibroid measured 3800 and 3220 mL, respectively. Two weeks post-UAE her caval filter was removed, via a jugular route, without complication. A follow up pelvic MRI, one month later, confirmed complete fibroid degeneration with migration of the fibroid into the endometrial cavity (Fig. 1). The uterus measured 2200 mL and the fibroid 1000 mL, correlating with a 42% and 69% respective relative reduction in size. At six weeks she passed a large ‘steak-sized’ degenerate fibroid. At three months pelvic ultrasound showed that the uterus had reduced to 315 mL and the fibroid volume was 1.5 mL. The patient has made a complete recovery and has been given life-long warfarin.

The association between deaths from myocardial infarction and household size in England and Wales.

Background Chronic infection with organisms such as Chlamydia pneumoniae is thought to cause coronary heart disease. We investigated whether myocardial infarction deaths are associated with large household size and overcrowding, as these are factors that may facilitate the transmission of infection. Design Ecological study of England and Wales. Methods Population data were obtained from the 1991 National Census and mortality data were obtained from the Office of National Statistics. For various categories of household size and overcrowding, we calculated mortality rates standardized for age, sex and deprivation. Results Standardized mortality rates for acute respiratory infections were associated with household size and overcrowding, while rates for myocardial infarction and gastric carcinoma, both putatively associated with chronic infection, were associated with household size. For combined deaths from causes other than myocardial infarction, there were small associations with household size and overcrowding. In the case of myocardial infarction, the association was generally strongest in the age group 45-54.9 years. For this age group, the standardized mortality rate ratio for the category of largest size household was 2.7 in the year 1991. Conclusions There is an association between household size and mortality from myocardial infarction. Chronic infection is a possible cause. J Cardiovasc Risk 2001, 8:159-163