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Biomedical subjects

Andrew E Ajani

Publications and source records attributed to Andrew E Ajani.

At least 19 recordsLinked to original sources
PubMed2006

The mystery of coronary artery spasm.

Coronary artery spasm is an important cause of chest pain and myocardial ischaemia. It can be defined as an exaggerated contractile response of epicardial coronary artery smooth muscle to various stimuli but the underlying mechanism is not well understood. Recent studies have shown that the loss of endothelial vasodilatory function in conjunction with an increase in vascular smooth muscle constrictor sensitivity to calcium are the likely predisposing conditions for coronary spasm. This review highlights current understanding of the pathophysiology, predisposing factors, diagnostic and therapeutic approaches for coronary spasm.

Coronary Vasospasm↗
PubMed2006

Use of drug-eluting stents in Victorian public hospitals.

OBJECTIVE: We aimed to assess the pattern of use of drug-eluting stents (DESs) in patients undergoing percutaneous coronary interventions (PCIs) in Victorian public hospitals. DESIGN, SETTING AND PATIENTS: Prospective study comparing the use of one or more DESs versus bare-metal stents (BMSs) only, in consecutive patients undergoing 2428 PCIs with stent implantation from 1 April 2004 to 31 December 2005 at seven Victorian public hospitals. MAIN OUTCOME MEASURES: Adherence to current Victorian Department of Human Services guidelines which recommend DES use in patients with high-risk features for restenosis (diabetes, small vessels, long lesions, in-stent restenotic lesions, chronic total occlusions and bifurcation lesions). RESULTS: Of the 2428 PCIs performed, at least one DES was implanted in 1101 (45.3%) and BMSs only were implanted in 1327 (54.7%). In 87.7% (966/1101) of PCI with DESs, there was at least one criterion for high risk of restenosis. DESs were more likely to be used in patients with diabetes (risk ratio [RR], 2.45; 95% CI, 2.02-2.97), small vessels (RR, 3.35; 95%CI, 2.35-4.76), long lesions (RR, 3.87; 95% CI, 3.23-4.65), in-stent restenotic lesions (RR, 3.98; 95%CI, 2.67-6.06), chronic total occlusions (RR, 1.30; 95% CI, 0.51-2.88) and bifurcation lesions (RR, 2.23; 95%CI, 1.57-3.17). However, 66.2% (1608/2428) of all PCIs were in patients eligible for DESs according to Victorian guidelines, and in 39.9% (642/1608) of these PCIs, a BMS was used. CONCLUSION: In Victorian public hospitals, DESs have been largely reserved for patients at high risk of restenosis in accordance with Department of Human Services guidelines. However, many patients with high-risk criteria for restenosis did not receive DESs. Greater use of DESs in these patients may improve outcomes by reducing the need for repeat revascularisation.

Angioplasty, Balloon, Coronary↗
PubMed2005

Incidence, location, magnitude, and clinical correlates of saphenous vein graft calcification: an intravascular ultrasound and angiographic study.

BACKGROUND: The pattern of saphenous vein graft (SVG) calcification before percutaneous intervention has not been studied. METHODS AND RESULTS: We used diagnostic and preintervention intravascular ultrasound (IVUS) to determine the incidence and magnitude of SVG calcification in 334 SVG lesions in 274 consecutive patients. Calcium was found in 133 SVGs (40%). Calcium was uniformly distributed among 48 lesion sites (14%), 43 proximal references (13%), and 42 distal references (13%). Calcium was superficial in 20 (40%) and deep in 28 (60%). Over the entire length of the SVGs, the maximum arc and length of calcium (in calcium-containing SVGs) averaged 174+/-107 degrees and 6.8+/-4.8 mm, respectively. In calcium-containing SVGs, lesion site arc and length of calcium measured 151+/-107 degrees and 4.1+/-3.7 mm, similar to the proximal and distal references (175+/-121 degrees and 4.0+/-2.3 mm and 177+/-121 degrees and 4.1+/-2.5 mm, respectively). Graft age (7.5+/-4.7 versus 10.5+/-4.7 years, P<0.0001), insulin-treated diabetes mellitus (40% versus 60%, P=0.02), and tobacco use (44% versus 55%, P=0.06) were clinical independent predictors of SVG calcification. CONCLUSIONS: Sixty-five percent of calcium-containing SVGs had reference calcium in the absence of lesion calcium. Calcium was located primarily in SVG wall and not at the plaque. These data suggest that SVG calcium is not just part of lesion formation and maturation. SVG calcium occurred more commonly in older grafts, in insulin-treated diabetic patients, and in smokers.

Aged↗
PubMed2005

Three-year follow-up after intravascular gamma-radiation for in-stent restenosis in saphenous vein grafts.

The Washington Radiation for In-Stent Restenosis Trial in Saphenous Vein Grafts (SVG WRIST) demonstrated safety and efficacy of intravascular radiation therapy (IRT) for the treatment of in-stent restenosis (ISR) in SVG at 12 months. In this study, we aimed to examine whether the safety and efficacy of IRT is durable up to 36 months. One hundred twenty patients with diffuse ISR in SVG underwent balloon angioplasty, laser or atherectomy ablation, and/or additional stenting. After successful intervention, patients were randomly assigned in a double-blind fashion to intravascular treatment with a ribbon containing either iridium (Ir)-192 (n = 60) or nonradioactive seeds (n = 60). The prescribed dose at 2 mm from the source was either 14 or 15 Gy in vessels 2.5-4.0 mm or 18 Gy in vessels > 4.0 mm in diameter. At 36 months, target lesion revascularization (TLR; 43% vs. 66%; P = 0.02) and target lesion revascularization-major adverse cardiac event (TLR-MACE; 49% vs. 71%; P = 0.02) rates continued to be lower in the IRT group, but both target vessel revascularization (TVR; 59% vs. 71%; P = 0.17) and TVR-MACE (63% vs. 77%; P = 0.11) rates were not. In SVG WRIST, patients with ISR treated with IRT had a marked reduction in the need for repeat TLR at 36 months, with sustained clinical benefit at 3 years despite late recurrences, which were more pronounced in the radiation group.

Aged↗
PubMed2005

Oral antiplatelet therapy and percutaneous coronary intervention.

The benefit of oral antiplatelet therapy following percutaneous coronary intervention (PCI) with intracoronary stent implantation is well established. Combined aspirin with clopidogrel or ticlopidine therapy is superior to aspirin alone in reducing thrombotic events after stent placement. Clopidogrel is the drug of choice, given that its efficacy is comparable to ticlopidine and it has a superior safety profile. Despite dual antiplatelet therapy, patients remain at risk of recurrent vascular events. Optimal timing, duration and dosage of antiplatelet therapy remain controversial. Recent evidence suggests additional benefit with clopidogrel pretreatment, high clopidogrel loading dose and long-term dual antiplatelet therapy post-PCI in high-risk patients.

Administration, Oral↗
PubMed2004

Oral rapamycin to inhibit restenosis after stenting of de novo coronary lesions: the Oral Rapamune to Inhibit Restenosis (ORBIT) study.

OBJECTIVES: The aim of this study was to establish safety and feasibility of oral Rapamycin at two doses-2 mg and 5 mg-in achieving low rates of repeat target lesion revascularization (TLR) in de novo native coronary artery lesions. BACKGROUND: Drug-eluting stents have shown the ability to limit restenosis. Oral Rapamycin is an alternative strategy that can target multiple coronary lesions suitable for treatment with any approved metal stent and at potentially lower cost. METHODS: The Oral Rapamune to Inhibit Restenosis (ORBIT) study is an open-label study of 60 patients with de novo lesions treated with bare metal stents in up to two vessels. After a loading dose of 5 mg, patients received a daily dose of 2 mg (n = 30) and 5 mg (n = 30) for 30 days. Six-month angiographic, intravascular ultrasound (IVUS), and clinical follow-up were conducted. RESULTS: Baseline clinical and procedural characteristics were similar: 10% of patients in the 2-mg group and 30% in the 5-mg group did not complete the course; 43% in the 2-mg group and 66% in the 5-mg group had side effects. At six-month follow-up, late loss (0.6 +/- 0.5 mm vs. 0.7 +/- 0.5 mm; p = NS), in-stent binary restenosis (7.1% vs. 6.9%; p = NS), in-stent percent volume obstruction by IVUS (29% vs. 24%; p = NS), and clinically driven TLR (14.3% vs. 6.9%; p = NS) were similar in 2-mg and 5-mg groups. CONCLUSIONS: Oral Rapamycin for the prevention of restenosis is safe, feasible, and associated with low rates of repeat revascularization. Although associated with certain side effects, it may be considered for patients undergoing multivessel stents if proven in larger randomized studies.

Administration, Oral↗
PubMed2004

Usefulness of periprocedural creatinine phosphokinase-MB release to predict adverse outcomes after intracoronary radiation therapy for in-stent restenosis.

We aimed to analyze periprocedural creatinine phosphokinase (CPK)-MB elevation in patients treated with intracoronary radiation therapy (IRT) for in-stent restenosis (ISR) to risk stratify these patients. The clinical significance of periprocedural CPK-MB elevation after IRT for ISR is unknown. An elevated CPK-MB has been associated with increased mortality after conventional angioplasty. We evaluated 1,326 patients who were enrolled in radiation trials for ISR at the Washington Hospital Center using gamma- and beta-emitters. Patients were analyzed according to degree of CPK-MB increase within 24 hours of the index IRT procedure (normal CPK-MB, CPK-MB 1 to 3 times the upper limit of normal, or CPK-MB >3 times the upper limit of normal). Patients with CPK-MB >3 times the upper limit of normal were older (64 +/- 12 years, p = 0.04), more likely to be smokers (64%, p = 0.04), hypertensive (85%, p <0.01), and diabetic (49%, p = 0.04). The cohort with the highest CPK-MB release (CPK-MB >3 times the upper limit of normal) had significantly higher rates of adverse clinical events at 12 months (major adverse cardiac events 40%, p <0.01), including death (9.3%, p <0.01) and late thrombosis (6.3%, p <0.01). Periprocedural CPK-MB elevation is of prognostic importance in patients treated with IRT for ISR, and its analysis appears to be mandatory to risk stratify these patients. The impact of glycoprotein IIb/IIIa antagonists in reducing periprocedural CPK-MB release awaits evaluation.

Aged↗
PubMed2004

Five-year follow-up after intracoronary gamma radiation therapy for in-stent restenosis.

BACKGROUND: The Washington Radiation for In-Stent Restenosis Trial is a double-blinded randomized study evaluating the effects of intracoronary radiation therapy (IRT) in patients with in-stent restenosis (ISR). METHODS AND RESULTS: One hundred thirty patients with ISR (100 native coronary and 30 vein grafts) underwent percutaneous transluminal coronary angioplasty, laser ablation, rotational atherectomy, or additional stenting (36% of lesions). Patients were randomized to either 192-Iridium IRT or placebo, with a prescribed dose of 15 Gy to a 2-mm radial distance from the center of the source. Angiographic restenosis (27% versus 56%, P=0.002) and target vessel revascularization (26% versus 68%, P<0.001) were reduced at 6 months in patients treated with IRT. Between 6 and 60 months, patients treated with IRT compared with placebo had more target lesion revascularization (IRT, 21.6% versus placebo, 4.7%; P=0.04) and target vessel revascularization (IRT, 21.5% versus placebo, 6.1%; P=0.03). At 5 years, the major adverse cardiac event rate was significantly reduced with IRT (46.2% versus 69.2%, P=0.008). CONCLUSIONS: In the Washington Radiation for In-Stent Restenosis Trial, patients with ISR treated with IRT using 192-Iridium had a reduction in the need for repeat target lesion and vessel revascularization at 6 months and 5 years.

Cardiac Catheterization↗
PubMed2004

Use of IIb/IIIa inhibitors in patients with in-stent restenosis treated with intracoronary gamma-radiation. Integrilin WRIST.

The Integrilin Washington Radiation for In-Stent Restenosis Trial (WRIST) aimed to study the impact of IIb/IIIa inhibitors as adjunct therapy to intracoronary radiation therapy (IRT) for patients with in-stent restenosis (ISR). The impact of GP IIb/IIIa inhibitor (eptifibatide) as adjunct therapy to vascular brachytherapy using (192)Ir emitter was examined in patients with in-stent restenosis. In the study, 150 patients were assigned to eptifibatide (Integrilin) and 150 patients to heparin only. Clinical composite endpoints at 30 days were similar between the patients treated with and without eptifibatide (4.7% vs. 4.0%; P = 0.78). There was a similarity in the non-Q-wave myocardial infarction (MI) rates between the eptifibatide and the control group. Major bleeding was similar in patients treated with and without eptifibatide. Overall, the use of eptifibatide as adjunct therapy for patients with ISR that are treated with IRT did not impact the clinical outcome at 30 days.

Aged↗
PubMed2004

Impact of radiation dose on late clinical outcome after intracoronary radiation therapy: three-year follow-up of Long WRIST.

To determine the safety and efficacy, including the impact, on the late recurrence rate of an incremental gamma-radiation dose from 15 to 18 Gy, we report the 3-year clinical outcome of Washington Radiation for In-Stent Restenosis Trial for Long Lesions (Long WRIST). One hundred eighty patients with recurrent in-stent restenosis (ISR) were enrolled in the Long WRIST series and treated with (192)Ir with 1 month of antiplatelet therapy. Between 6 months and 3 years, the need for repeat revascularization was low and similar among the three groups. At 3 years, target lesion revascularization (TLR) and major adverse cardiac events (MACE) were less frequent in the 18 Gy group than in the 15 Gy group (P = 0.12 for TLR, P < 0.05 for MACE) and less frequent in the 15 Gy group as compared to the placebo group (P < 0.05 for TLR and MACE). At 3 years, a higher dose of 18 Gy with (192)Ir continues to improve the outcome of patients treated for ISR when compared to patients treated with 15 Gy or placebo.

Analysis of Variance↗
PubMed2004

Major noncardiac surgery following coronary stenting: when is it safe to operate?

The optimal timing for elective noncardiac surgery (NCS) after coronary stenting is uncertain. We identified 47 patients who underwent elective NCS within 90 days of coronary stent placement between January 1995 and December 2000. Twenty-seven patients had NCS within 3 weeks of coronary stenting. Six of the seven in whom thienopyridine antiplatelet therapy was discontinued died postoperatively in a manner suggestive of stent thrombosis. In contrast, only 1 of the 20 patients in whom the thienopyridine was continued through the NCS died. The frequency of perioperative hemorrhage was similar whether or not the antiplatelet agent was continued. Only 1 perioperative death occurred in the 20 patients with NCS more than 3 weeks following stenting.

Aged↗
PubMed2004

Intravascular ultrasound predictors of subacute vessel closure after balloon angioplasty or atherectomy.

BACKGROUND: Factors leading to subacute vessel closure after percutaneous coronary intervention (PCI) have not been well established in lesions treated with balloon angioplasty or atherectomy. METHODS AND RESULTS: We used intravascular ultrasound (IVUS) to determine the pre- and post-PCI characteristics involved in subacute vessel closure after PCI. Of 3,403 patients undergoing IVUS imaging during coronary balloon angioplasty or atherectomy, 8 patients (0.2%) developed angiographically documented subacute vessel closure within 1 week post-PCI and were compared to a group matched by procedure date (within 6 months), age, gender, stable or unstable angina, lesion location and treatment (balloon angioplasty or atherectomy). IVUS identified at least one cause for subacute vessel closure in 87% of patients (vs 25% in matched lesions, p < 0.01). Causes were all procedure-related and included inadequate final lumen (60%), dissection (50%) and thrombus (25%). Pre-procedure lesion characteristics were not different from matched lesions. CONCLUSIONS: Subacute vessel closure after balloon angioplasty or atherectomy is mostly related to insufficient post-procedure lumen dimension or dissection.

Aged↗
PubMed2003

Repeat intracoronary radiation for recurrent in-stent restenosis in patients who failed intracoronary radiation.

BACKGROUND: Intracoronary radiation therapy (IRT) is the only proven treatment for in-stent restenosis (ISR). It is, however, associated with a significant failure rate. The present study evaluated the outcomes of patients who underwent repeat intracoronary radiation for recurrent ISR. METHODS AND RESULTS: Fifty-one consecutive patients who failed a previous radiation treatment, presented with angina and angiographic evidence of ISR, and were treated with percutaneous coronary intervention (PCI) and repeat radiation to the same segment were studied. Twenty-five patients were treated with gamma radiation in a dose of 15 Gy, and 26 were treated with beta radiation doses of 18.3 to 23 Gy. The mean cumulative dose for this cohort was 39.5+/-11.9 Gy (range, 29 to 75.6 Gy). The outcomes of those patients were compared with outcomes of 299 patients who also failed initial radiation but were treated with repeat conventional PCI to a previously irradiated segment without repeat radiation. At 9 months after treatment, the repeat-IRT group had lower rates of target lesion revascularization (23.5% versus 54.6%; P<0.001) and major adverse cardiac events, including target vessel revascularization (29.4% versus 61.3%; P<0.001). At 9 months, patients with repeat IRT were free of angiographic and clinical events related to the radiation therapy. CONCLUSIONS: Repeat gamma or beta radiation to treat failed IRT for ISR after conventional PCI is safe and effective at 9 months and should be considered as a therapeutic option for this difficult patient subset.

Angina Pectoris↗
PubMed2003

Time course of stent endothelialization after intravascular radiation therapy in rabbit iliac arteries.

BACKGROUND: Late total occlusion after vascular brachytherapy (VBT) continues to be a serious complication. Delayed reendothelialization was suggested as a pivotal cause, but the time course for complete healing is unknown. METHODS AND RESULTS: Seventy-two rabbit iliac arteries underwent stent implantation and were treated with gamma-radiation using 192Ir. The prescribed doses were 0 Gy (controls, n=24 arteries), 15 Gy (n=24), or 30 Gy (n=24) at 2 mm. Animals were killed at 1 month (n=24), 3 months (n=24), or 6 months (n=24) and were analyzed for histomorphometry or scanning electron microscopy. Intimal area was reduced after VBT at 3 months with 15 and 30 Gy (0.66+/-0.07 and 0.66+/-0.04 mm2, respectively) compared with controls (1.01+/-0.11 mm2, P<0.05) and at 6 months with 30 Gy (0.75+/-0.09 versus 1.28+/-0.26 mm2 in controls, P<0.01). Intimal area was similar at 6 months between 15 Gy and controls. At 1 month, 92+/-4% of the control stented segment was covered with endothelial cells, whereas only 37+/-4% and 37+/-8% was covered in the 15- and 30-Gy arteries, respectively. Similarly, at 3 and 6 months, there was a difference in the extent of reendothelialized areas (at 3 months, 95+/-2%, 32+/-12%, and 29+/-13%; and at 6 months, 98+/-2%, 40+/-8%, and 35+/-12% in control, 15-Gy, and 30-Gy arteries, respectively). Excess platelets and leukocytes were seen in irradiated arteries without complete coverage of endothelium. CONCLUSIONS: Reendothelialization after VBT is not completed at 6 months after VBT. Special care with prolonged antiplatelet therapy should be considered beyond that time point.

Animals↗
PubMed2003

Intracoronary radiation therapy improves the clinical and angiographic outcomes of diffuse in-stent restenotic lesions: results of the Washington Radiation for In-Stent Restenosis Trial for Long Lesions (Long WRIST) Studies.

BACKGROUND: The Washington Radiation for In-Stent Restenosis Trial for long lesions (Long WRIST) was designed to determine the safety and efficacy of vascular brachytherapy for the treatment of diffuse in-stent restenosis. METHODS AND RESULTS: A total of 120 patients with diffuse in-stent restenosis in native coronary arteries (lesion length, 36 to 80 mm) were randomized for either radiation with 192Ir with 15 Gy at 2 mm from the source axis or placebo. After enrollment, 120 additional patients with the same inclusion criteria were treated with 192Ir with 18 Gy and included in the Long WRIST High Dose registry. Antiplatelet therapy was initially prescribed for 1 month and was extended to 6 months in the last 60 patients of the Long WRIST High Dose registry. At 6 months, the binary angiographic restenosis rate was 73%, 45%, and 38% in the placebo, 15 Gy, and 18 Gy radiated groups, respectively (P<0.05). At 1 year, the primary clinical end point of major cardiac events was 63% in the placebo group and 42% in the radiated group with 15 Gy (P<0.05). The major cardiac event rate was further reduced with 18 Gy (22%; P<0.05 versus 15 Gy). Late thrombosis was 12%, 15%, and 9% in the placebo group, 15 Gy group with 1 month of antiplatelet therapy, and 18 Gy group with 6 months of antiplatelet therapy, respectively. CONCLUSIONS: Vascular brachytherapy with 192Ir is safe and reduces the rate of recurrent restenosis in diffuse in-stent restenosis. The efficacy of vascular brachytherapy on angiographic and clinical outcomes is enhanced with a radiation dose of 18 Gy and prolonged antiplatelet therapy.

Brachytherapy↗