Effect of sex on sodium-glucose co-transporter-2 antagonists and glucagon-like peptide-1 agonists in heart failure.

BACKGROUND: Recent evidence suggests that medications not primarily targeting the cardiovascular (CV) system may have cardioprotective effects in patients with heart failure (HF), in particular the anti-diabetic therapies sodium-glucose co-transporter-2 (SGLT-2) antagonists and glucagon-like peptide-1 (GLP-1) agonists. We conducted a systematic review to assess the pooled evidence for the use of SGLT-2 antagonists and GLP-1 agonists in patients with HF and the effect of biological sex on the results. METHODS: MEDLINE, Embase, Cochrane Library and clinical trial databases were searched until February 2023. Randomized controlled trials (RCTs) published in English that included adult participants with HF who were randomized to an SGLT-2 antagonist or GLP-1 agonist with a primary or secondary outcome of HF hospitalization (HFH) or CV death were eligible for inclusion. Data pooling was undertaken using a random effects model and odds ratios (ORs) to determine the association between drug and outcome. Sub-group analyses to investigate sex differences were conducted. RESULTS: Six RCTs were included (24 781 patients). Four studies investigated SGLT-2 antagonists, and two studies examined GLP-1 agonists. SGLT-2 antagonists improved HFH {OR [95% confidence interval (CI)]: 0.69 [0.63, 0.77], P < 0.001} and CV death [0.87 (0.78, 0.97), P = 0.01] independent of diabetes status, with excellent homogeneity across all four studies. No beneficial effects were found for GLP-1 agonists. The effects of SGLT-2 antagonists on HFH and CV death were similar in men and women [OR (95% CI): HFH, 0.70 (0.64, 0.76), P < 0.001 and 0.58 (0.46, 0.74), P < 0.001, respectively; CV death, 0.86 (0.78, 0.95), P = 0.003 and 0.84 (0.73, 0.96), P = 0.01, respectively], and the neutral effect of GLP-1 agonists on HFH and CV death was similar in men and women (all P > 0.05). CONCLUSIONS: SGLT-2 antagonists but not GLP-1 agonists beneficially affect HFH and CV death in patients with HF with or without diabetes. We show for the first time that GLP-1 agonists have a neutral effect on HFH and CV death in both male and female HF patients and a reduction in HFH and CV death in male and female HF patients taking SGLT-2 antagonists.

Recall of Autobiographical Memories Following Odor vs Verbal Cues Among Adults With Major Depressive Disorder.

Importance: Major depressive disorder (MDD) is associated with deficits in autobiographical memory (AM) recall, which is thought to stem from disruptions in effortful recall. Understanding whether these deficits are mitigated when recall is stimulated more directly, such as by odor cues, could inform therapeutic interventions for MDD. Objective: To evaluate whether deficits in specific AM recall in MDD are mitigated when odor cues vs word cues are used to prompt memory. Design, Setting, and Participants: This cross-sectional study assessed recall of specific AMs in response to both odor cues and word cues (in a randomized, counterbalanced order) in a repeated measures design. Data were collected between September 2021 and November 2022. The study took place at the University of Pittsburgh School of Medicine in Pennsylvania and included adults with a primary diagnosis of MDD, according to the Mini International Neuropsychiatric Interview. Data were analyzed from January to June 2023. Main Outcomes and Measures: The primary outcome measure was the percentage of specific AMs recalled in response to odor-cued memories vs word-cued memories. Additional outcome measures included ratings of arousal, vividness, repetition, and recall response time for odor-cued memories vs word-cued memories. Results: Thirty-two adults (mean [SD] age, 30.0 [10.1] years; 26 [81.3%] female; 6 [18.8%] male) with a primary diagnosis of MDD completed the study. Participants recalled more specific AMs for odor cues than word cues (mean [SD], 68.4% [20.4%] vs 52.1% [23.3%]; Cohen d, 0.78; P < .001). Additionally, odor-cued recall was rated more arousing (mean [SD], 3.0 [0.8] vs 2.6 [0.7]; Cohen d, 1.28; P < .001) and vivid (mean [SD], 3.3 [0.7] vs 3.0 [0.7]; Cohen d, 0.67; P < .001), and was slower than word-cued recall (mean [SD], 14.5 [3.6] vs 8.9 [3.4] seconds; Cohen d, 1.18; P < .001). When compared with the population mean for word cues in healthy controls (80%), participants recalled fewer specific memories in response to words (Cohen d, 1.18; P < .001), supporting the presence of overgenerality. Notably, the percentage of specific memories recalled in response to odor cues did not differ from the healthy control population mean (Cohen d, 0.26; P = .15). Conclusions and Relevance: In this cross-sectional study, adults with MDD recalled more specific AMs in response to odor cues compared with word cues. This study suggests that AM deficits may only be observed when verbal cues are used and provides a potential new method for increasing specific AM recall in patients with MDD.

Medical management of anginal symptoms in women with stable angina pectoris: A systematic review of randomised controlled trials.

BACKGROUND: Medical therapies are used to improve stable anginal symptoms and quality of life in clinical practice however the evidence for the use of antianginal medication in women is largely unknown. We conducted a systematic review to investigate the extent of the evidence-base for the medical management of anginal symptoms in women with stable angina. METHODS: MEDLINE, EMBASE, Cochrane and ClinicalTrials.gov databases were searched to the end of December 2019. Retrieved papers were hand searched. Included were randomised controlled trials with at least one week of follow-up that included women with stable angina pectoris, with or without significant coronary atherosclerosis, randomised to conventional antianginal medication or/and a comparator, with a primary or secondary endpoint of angina frequency or glyceryl trinitrate (GTN) consumption. RESULTS: A total of 397 eligible publications were included in a qualitative analysis, with women comprising up to 20-30% of the study populations. No publication that included women and men reported all data separately for each sex. Twenty-six publications reported any female data separately from male data but only 18 reported angina data for women, 12 of which included fewer than 10 women. CONCLUSIONS: Substantially fewer women than men were included in randomised trials of antianginal medications reporting effects on anginal symptoms, and reporting of data by sex was infrequent. As a result, there is little evidence on which to base treatment recommendations for anginal symptoms in women. Our results provide a platform for future studies to fill this void in the evidence.

Thromboprophylaxis with rivaroxaban in patients with malignancy and central venous lines (TRIM-Line): A two-center open-label pilot randomized controlled trial.

BACKGROUND: Central venous catheter (CVC) insertion is an important risk factor for venous thromboembolism (VTE) among patients with cancer. Routine use of primary thromboprophylaxis in this patient population is not currently recommended. We sought to assess the feasibility of conducting a randomized controlled trial (RCT) assessing the safety and efficacy of rivaroxaban (10 mg daily) to prevent VTE complications in this patient population. METHODS: This is a two-center prospective, randomized, open blinded end point pilot trial including patients with active cancer and a newly inserted CVC. Patients were randomly assigned 1:1 to rivaroxaban or observation for 90 days. The primary feasibility outcome of this pilot study was the number of participants recruited per month. Secondary clinical outcomes included thrombotic complications, major VTE, and major bleeding episodes. RESULTS: Overall, 105 patients were enrolled over 11 months. The average enrollment rates were 7.5 and 2 patients per month at the two participating centers, respectively. Overall, thrombotic complications occurred in 3 patients in the rivaroxaban group (5.8%; 95% confidence interval [CI], 1.2-16.0) compared with 5 patients in the control group (9.4%; 95% CI, 3.1-20.7) (HR, 0.58; 95% CI, 0.14-2.5). Major VTE occurred in 2 (3.9%; 95% CI, 0.5-13.2) and 3 (5.7%; 95% CI, 1.2-15.7) patients in the rivaroxaban and control group, respectively (HR, 0.66; 95% CI, 0.11-3.9). One patient (1.9%) receiving rivaroxaban had a major bleeding event. CONCLUSIONS: Thrombotic complications are common in patients with cancer and a newly inserted CVC. The pilot trial achieved its enrollment targets and supports that a large multicenter RCT is feasible in this area. ClinicalTrials.gov (NCT03506815).

Association of Radial Artery Graft vs Saphenous Vein Graft With Long-term Cardiovascular Outcomes Among Patients Undergoing Coronary Artery Bypass Grafting: A Systematic Review and Meta-analysis.

Importance: Observational studies have suggested that the use of radial artery grafts for coronary artery bypass grafting may improve clinical outcomes compared with the use of saphenous vein grafts, but this has not been confirmed in randomized trials. Objective: To compare clinical outcomes between patients receiving radial artery vs saphenous vein grafts for coronary artery bypass grafting after long-term follow-up. Design, Setting, and Participants: Patient-level pooled analysis comparing radial artery vs saphenous vein graft in adult patients undergoing isolated coronary artery bypass grafting from 5 countries (Australia, Italy, Serbia, South Korea, and the United Kingdom), with enrollment from 1997 to 2009 and follow-up completed in 2019. Interventions: Patients were randomized to undergo either radial artery (n = 534) or saphenous vein (n = 502) grafts for coronary artery bypass grafting. Main Outcomes and Measures: The primary outcome was a composite of death, myocardial infarction, or repeat revascularization and the secondary outcome was a composite of death or myocardial infarction. Results: A total of 1036 patients were randomized (mean age, 66.6 years in the radial artery group vs 67.1 years in the saphenous vein group; 376 [70.4%] men in the radial artery group vs 351 [69.9%] in the saphenous vein group); 942 (90.9%) of the originally randomized patients completed 10 years of follow-up (510 in the radial artery group). At a median (interquartile range) follow-up of 10 (10-11) years, the use of the radial artery, compared with the saphenous vein, in coronary artery bypass grafting was associated with a statistically significant reduction in the incidence of the composite outcome of death, myocardial infarction, or repeat revascularization (220 vs 237 total events; 41 vs 47 events per 1000 patient-years; hazard ratio, 0.73 [95% CI, 0.61-0.88]; P < .001) and of the composite of death or myocardial infarction (188 vs 193 total events; 35 vs 38 events per 1000 patient-years; hazard ratio, 0.77 [95% CI, 0.63-0.94]; P = .01). Conclusions and Relevance: In this individual participant data meta-analysis with a median follow-up of 10 years, among patients undergoing coronary artery bypass grafting, the use of the radial artery compared with the saphenous vein was associated with a lower risk of a composite of cardiovascular outcomes.

Angiographic Outcome of Coronary Artery Bypass Grafts: The Radial Artery Database International Alliance.

BACKGROUND: We used a large patient-level data set including 6 angiographic randomized controlled trials (RCTs) on coronary artery bypass conduits to explore incidence and determinants of coronary graft failure. METHODS: Patient-level angiographic data of 6 RCTs comparing long-term outcomes of the radial artery and other conduits were joined. Primary outcome was graft occlusion at maximum follow-up. The analysis was divided as (1) left anterior descending coronary (LAD) distribution and (2) non-LAD distribution (circumflex and right coronary artery). Mixed-model multivariable Cox regression including all baseline characteristics with stratification by individual trials was used to identify predictors of graft occlusion. RESULTS: Included were 1091 patients and 2281 grafts, consisting of 921 left internal mammary arteries, 74 right internal mammary arteries, 710 radial arteries, and 576 saphenous veins. All left internal mammary arteries were used on the LAD, the other conduits were used on the non-LAD distribution. Mean angiographic follow up was 65 ± 29 months. Occlusion rates were 2.3% for the left internal mammary arteries, 13.5% for the left internal mammary arteries, 9.4% for the right internal mammary arteries, and 17.5% for the saphenous veins. At multivariable analysis, type of conduit used, age, female sex, left ventricular ejection fraction of less than 0.50, and use of the Y graft were significantly associated with graft occlusion in the non-LAD distribution. CONCLUSIONS: Our analyses showed that failure of the left internal mammary arteries-to-LAD bypass is a very uncommon event. For the non-LAD distribution, the nonuse of radial artery, age, female sex, left ventricular ejection fraction of less than 0.50, and use of the Y graft configuration were significantly associated with midterm graft failure.

The RADial artery International ALliance (RADIAL) extended follow-up study: rationale and study protocol.

It is generally accepted that radial artery (RA) grafts have better mid-term patency rate compared to saphenous vein grafts. However, the clinical correlates of the improved patency rate are still debated. Observational studies have suggested increased survival and event-free survival for patients who receive an RA rather than a saphenous vein, but they are open to bias and confounders. The only evidence based on randomized data is a pooled meta-analysis of 6 randomized controlled trial comparing the RA and the saphenous vein published by the RADial artery International Alliance (RADIAL). In the RADIAL database, improved freedom from follow-up cardiac events (death, myocardial infarction and repeat revascularization) was found at 5-year follow-up in the RA arm. The most important limitation of the RADIAL analysis is that most of the included trials had an angiographic follow-up in the first 5 years and it is unclear whether the rate of repeat revascularization (the main driver of the composite outcome) was clinically indicated due to per-protocol angiographies. Here, we present the protocol for the long-term analysis of the RADIAL database. By extending the follow-up beyond the 5th postoperative year (all trials except 1 did not have angiographic follow-up beyond 5 years), we aim to provide data on the role of RA in coronary artery bypass surgery with respect to long-term outcomes.

Long-term performance of an external stent for saphenous vein grafts: the VEST IV trial.

BACKGROUND: Externally stenting saphenous vein grafts reduces intimal hyperplasia, improves lumen uniformity and reduces oscillatory shear stress 1 year following surgery. The present study is the first to present the longer-term (4.5 years) performance and biomechanical effects of externally stented saphenous vein grafts. METHODS: Thirty patients previously implanted with the VEST external stent in the randomized, within-patient-controlled VEST I study were followed up for adverse events; 21 of these were available to undergo coronary angiography and intravascular ultrasound. RESULTS: Twenty-one stented and 29 nonstented saphenous vein grafts were evaluated by angiography and ultrasound at 4.5 ± 0.3 years. Vein graft failure rates were comparable between stented and nonstented grafts (30 and 23% respectively; p = 0.42). All failures were apparent at 1 year except for one additional nonstented failure at 4.5 years. In patent vein grafts, Fitzgibbon perfect patency remained significantly higher in the stented versus nonstented vein grafts (81 and 48% respectively, p = 0.002), while intimal hyperplasia area (4.27 mm2 ± 1.27 mm2 and 5.23 mm2 ± 1.83 mm2 respectively, p < 0.001) and thickness (0.36 mm ± 0.09 mm and 0.42 mm ± 0.11 mm respectively, p < 0.001) were significantly reduced. Intimal hyperplasia proliferation correlated with lumen uniformity and with the distance between the stent and the lumen (p = 0.04 and p < 0.001 respectively). CONCLUSIONS: External stenting mitigates saphenous vein graft remodeling and significantly reduces diffuse intimal hyperplasia and the development of lumen irregularities 4.5 years after coronary artery bypass surgery. Close conformity of the stent to the vessel wall appears to be an important factor. TRIAL REGISTRATION: NCT01415245 . Registered 11 August 2011.

Role of Testosterone in the Treatment of Cardiovascular Disease.

Cardiovascular disease (CVD) is the most prevalent non-communicable cause of death worldwide. Testosterone is a sex hormone that is predominant in males but also occurs in lower concentrations in females. It has effects directly on the blood vessels of the cardiovascular system and on the heart, as well as effects on risk factors for CVD. Serum testosterone concentrations are known to decrease with age and reduced testosterone levels are linked to premature coronary artery disease, unfavourable effects on CVD risk factors and increased risk of cardiovascular mortality independent of age. A significant number of men with heart failure demonstrate reduced serum testosterone concentrations and there is early evidence suggesting that low testosterone levels affect cardiac repolarisation. Any association between endogenous testosterone concentrations and CVD in women has yet to be established. Testosterone replacement is used to treat men with hypogonadism but also has cardiovascular effects. This review will present the current evidence, expert opinion and controversies around the role of testosterone in the pathophysiology of CVD and surrounding the use of testosterone treatment and its effects on the cardiovascular system and CVD.

OCT imaging of aorto-coronary vein graft pathology modified by external stenting: 1-year post-surgery.

AIMS: The Venous External Support Trial (VEST) evaluated whether a novel external stent attenuated saphenous vein graft (SVG) disease assessed with intravascular ultrasound 1 year following coronary artery bypass graft (CABG) surgery. This sub-study assessed SVGs with and without external stenting using optical coherence tomography (OCT). The aim of this study was to accurately compare quantitative and qualitative features of SVGs with and without a novel external stent using OCT. METHODS AND RESULTS: Twenty-four of 30 patients (65 ± 8 years) enrolled in VEST underwent coronary angiography with OCT imaging using a non-occlusive technique. Quantitative analysis of lumen area was performed in one frame every 10 mm along the length of the graft, from distal to proximal anastomosis, and pathological features within the lumen were noted. Mean cross-sectional area was greater in unstented vs. stented grafts (8.4 ± 3 vs. 7.6 ± 2.7 mm; P = 0.005). The lumen of the stented grafts was more homogeneous (difference between maximum and minimum lumen diameter was significantly smaller in stented compared with unstented grafts, 0.28 ± 0.19 vs. 0.33 ± 0.23 mm, respectively, P = 0.006), and more circular (mean eccentricity index 0.08 ± 0.06 vs. 0.10 ± 0.06, stented vs. unstented; P = 0.019). Adherent thrombus was identified in three grafts (all unstented). CONCLUSION: Our findings highlight the early changes occurring in SVGs after implantation of aorto-coronary bypass conduits, changes that may accelerate vein graft failure. External stenting resulted in a more homogeneous and less eccentric lumen with no thrombus formation.

Flow patterns in externally stented saphenous vein grafts and development of intimal hyperplasia.

BACKGROUND: Low and oscillatory wall shear stress promotes endothelial dysfunction and vascular disease. The aim of the study was to investigate the impact of an external stent on hemodynamic flow parameters in saphenous vein grafts (SVGs) and their correlation with the development of intimal hyperplasia. METHODS: We performed post hoc computational fluid dynamics analysis of the randomized Venous External Support Trial, in which angiography and intravascular ultrasound data were available for 29 patients, 1 year after coronary artery bypass grafting. Each patient received 1 external stent, to either the right or left coronary territories; ≥ 1 patients with nonstented SVGs served as control(s). Diffuse flow patterns were assessed using mean values of various hemodynamic parameters, including time-averaged wall shear stress and oscillatory shear index (OSI). Focal flow disturbances were characterized using percentile analysis of each parameter. RESULTS: Angiography and intravascular ultrasound data were available for 53 and 43 SVGs, respectively. The stented versus nonstented SVG failure rates were significantly lower in the left territory (17.6% vs 27.5%; P = .02), and significantly higher in the right territory (46.2% vs 13.4%; P = .01). In both diffuse and focal flow-pattern analyses, OSI was significantly lower in the stented versus nonstented SVG group (P = .009 and P < .003, respectively), whereas no significant differences were observed in time-averaged wall shear stress values. High OSI values were correlated with the development of intimal hyperplasia (P = .01). CONCLUSIONS: External stenting affects SVG's hemodynamics 1 year after coronary artery bypass grafting and may mitigate the progression of intimal hyperplasia by reducing oscillatory shear stress.

A Randomized Trial of External Stenting for Saphenous Vein Grafts in Coronary Artery Bypass Grafting.

BACKGROUND: External stents inhibit saphenous vein graft (SVG) intimal hyperplasia in animal studies. We investigated whether external stenting inhibits SVG diffuse intimal hyperplasia 1 year after coronary artery bypass graft surgery. METHODS: Thirty patients with multivessel disease undergoing coronary artery bypass graft surgery were enrolled. In addition to an internal mammary artery graft, each patient received one external stent to a single SVG randomly allocated to either the right or left coronary territories; and one or more nonstented SVG served as the control. Graft patency was confirmed at the end of surgery in all patients. The primary endpoint was SVG intimal hyperplasia (mean area) assessed by intravascular ultrasonography at 1 year. Secondary endpoints were SVG failure, ectasia (>50% initial diameter), and overall uniformity as judged by Fitzgibbon classification. RESULTS: One-year follow-up angiography was completed in 29 patients (96.6%). All internal mammary artery grafts were patent. Overall SVG failure rates did not differ significantly between the two groups (30% stented versus 28.2% nonstented SVG, p = 0.55). The SVG mean intimal hyperplasia area, assessed in 43 SVGs, was significantly reduced in the stented group (4.37 ± 1.40 mm(2)) versus nonstented group (5.12 ± 1.35 mm(2), p = 0.04). In addition, stented SVGs demonstrated marginally significant improvement in lumen uniformity (p = 0.08) and less ectasia (6.7% versus 28.2%, p = 0.05). There was some evidence that ligation of side branches with metallic clips increased SVG failure in the stented group. CONCLUSIONS: External stenting has the potential to improve SVG lumen uniformity and reduce diffuse intimal hyperplasia 1 year after coronary artery bypass graft surgery.

Cardiac rehabilitation to improve physical functioning in refractory angina: a pilot study.

OBJECTIVES: Refractory angina patients suffer debilitating chest pain despite optimal medical therapy and previous cardiovascular intervention. Cardiac rehabilitation is often not prescribed due to a lack of evidence regarding potential efficacy and patient suitability. A randomised controlled study was undertaken to explore the impact of cardiac rehabilitation on cardiovascular risk factors, physical ability, quality of life and psychological morbidity among refractory angina sufferers. METHODS: Forty-two refractory angina patients (65.1 ± 7.3 years) were randomly assigned to an 8-week Phase III cardiac rehabilitation program or symptom diary control. Physical assessment, Progressive Shuttle Walk test, Hospital Anxiety and Depression Scale, Health Anxiety Questionnaire, the York Angina Beliefs scale, ENRICHD Social Support Instrument and SF-36 were completed before and after intervention and at 8-week follow-up. RESULTS: Following cardiac rehabilitation, patients demonstrated improved physical ability compared with controls in Progressive Shuttle Walk level attainment (p = 0.005) and total distance covered (p = 0.015). Angina frequency and severity remained unchanged in both groups, with the control demonstrating worsening SF-36 pain scale (63.43 ± 22.28 vs. 55.46 ± 23.98, p = 0.025). Cardiac rehabilitation participants showed improved Health Anxiety Questionnaire reassurance (1.71 ± 1.72 vs. 1.14 ± 1.23, p = 0.026) and York Beliefs anginal threat perception (12.42 ± 4.58 vs. 14.35 ± 4.73, p = 0.05) after cardiac rehabilitation. Physical measures were broadly unaffected. CONCLUSIONS: Cardiac rehabilitation can be prescribed to improve physical ability without affecting angina frequency or severity among patients with refractory angina.

Vascular reactivity and flow characteristics of radial artery and long saphenous vein coronary bypass grafts: a 5-year follow-up.

BACKGROUND: Radial artery (RA) aortocoronary bypass grafts anastomosed to a branch of the circumflex coronary artery have significantly better patency rates than saphenous vein (SV) grafts at 5 years, but the physiological characteristics and mechanisms involved are not clearly defined. We compared RA and SV graft vasomotor and flow responses to endothelium-dependent and -independent stimuli 5 years after surgery in a subgroup of patients enrolled in the Radial artery versus Saphenous Vein Patency (RSVP) trial. METHODS AND RESULTS: Twenty-seven patients were included in the study (RA, n=15; SV, n=12). Graft blood flow was calculated from flow velocity, measured by intracoronary Doppler, and luminal diameter, measured by quantitative coronary angiography, before and after intragraft infusions of adenosine, acetylcholine, and isosorbide dinitrate. At rest, RA luminal diameters were significantly smaller than SV luminal diameters (P=0.029), blood flow velocity was greater in RA than SV (P=0.008), and volume blood flows were similar. RA but not SV dilated in response to adenosine and isosorbide dinitrate (all P<0.05, RA versus SV, percent change from baseline), and there were no significant differences in the diameter responses to acetylcholine. Volume blood flow responses to adenosine, acetylcholine, and isosorbide dinitrate were comparable. CONCLUSIONS: Five years after surgery, RA coronary bypass conduits grafted to a single coronary territory demonstrated preserved flow-mediated vasodilatation, whereas SV grafts did not. Our results may provide insight into the more favorable patency of RA grafts over SV grafts. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00139399.

Testosterone and coronary artery disease in men.

Coronary artery disease (CAD) is the leading cardiovascular cause of death, and in men, endogenous testosterone concentrations are inversely related to the extent and severity of CAD. Testosterone is known to affect a number of risk factors for CAD and has effects on vascular tone, vasoreactivity and blood flow of blood vessels beyond the reproductive system, indicating that testosterone may be involved in the pathogenesis of CAD. In this review we will present and discuss the actions of endogenous testosterone and testosterone treatment on risk factors for CAD, on the blood vessel wall and blood flow, and on atheroma development and progression, and discuss the potential for testosterone use in men with CAD.

Radial artery versus saphenous vein patency randomized trial: five-year angiographic follow-up.

BACKGROUND: Graft patency is a fundamental predictor of long-term survival after coronary artery bypass surgery. Left and right internal thoracic artery (arterial) graft patency has been shown to be superior to that of saphenous vein grafts. More recently, the radial artery has been used as an aortocoronary graft, but little is known about the midterm and long-term patency of this conduit. We performed a single-center prospective randomized trial comparing the angiographic patency of radial artery and saphenous vein aortocoronary bypass grafts at 5 years after surgery. METHODS AND RESULTS: We enrolled 142 patients randomized at a single center to have either the radial artery or saphenous vein grafted to a stenosed branch of the native left circumflex coronary artery. The primary end point was angiographic graft patency 5 years postoperatively. At 5 years, 134 patients were alive and eligible for reangiography (5-year survival, 94.4%). Angiography was performed in 103 patients (77%); 98.3% of radial artery grafts and 86.4% of saphenous vein grafts were patent (P=0.04). Graft narrowing occurred in 10% of patent radial artery grafts and 23% of patent saphenous vein grafts (P=0.01). CONCLUSIONS: Radial artery aortocoronary bypass grafts to a stenosed branch of the circumflex coronary artery have an excellent patency rate at 5 years. This was significantly better than the patency rate for saphenous vein grafts and comparable to reported patency rates for internal thoracic artery grafts.

Coronary vasomotor and blood flow responses to isoflavone-intact soya protein in subjects with coronary heart disease or risk factors for coronary heart disease.

Results in animals suggest favourable coronary vasomotor actions of isoflavones; however, the effects of isoflavones on the human coronary circulation have not been determined. In the present study, we therefore investigated the effects of short-term isoflavone-intact soya protein ingestion on basal coronary arterial tone and stimulated vasoreactivity and blood flow in patients with CHD (coronary heart disease) or risk factors for CHD. Seventy-one subjects were randomized, double-blind, to isoflavone-intact soya protein [active; n=33, aged 58+/-8 years (mean+/-S.D.)] or isoflavone-free placebo (n=38, aged 61+/-8 years) for 5 days prior to coronary angiography. In 25 of these subjects, stimulated coronary blood flow was calculated from flow velocity, measured using intracoronary Doppler and coronary luminal diameter before and after intracoronary adenosine, ACh (acetylcholine) and ISDN (isosorbide dinitrate) infusions. Basal and stimulated coronary artery luminal diameters were measured using quantitative coronary angiography. Serum concentrations of the isoflavones genistein, daidzein and equol were increased by active treatment (P<0.001, P<0.001 and P=0.03 respectively). Basal mean luminal diameter was not significantly different between groups (active compared with placebo: 2.9+/-0.7 compared with 2.73+/-0.44 mm, P=0.31). There was no difference in luminal diameter, flow velocity and volume flow responses to adenosine, ACh or ISDN between groups. Active supplement had no effect on basal coronary artery tone or stimulated coronary vasoreactivity or blood flow compared with placebo. Our results suggest that short-term consumption of isoflavone-intact soya protein is neither harmful nor beneficial to the coronary circulation of humans with CHD or risk factors for CHD. These results are consistent with recent cautions placed on the purported health benefits of plant sterols.

Effects of oral testosterone treatment on myocardial perfusion and vascular function in men with low plasma testosterone and coronary heart disease.

Intracoronary testosterone infusions induce coronary vasodilatation and increase coronary blood flow. Longer term testosterone supplementation favorably affected signs of myocardial ischemia in men with low plasma testosterone and coronary heart disease. However, the effects on myocardial perfusion are unknown. Effects of longer term testosterone treatment on myocardial perfusion and vascular function were investigated in men with CHD and low plasma testosterone. Twenty-two men (mean age 57 +/- 9 [SD] years) were randomly assigned to oral testosterone undecanoate (TU; 80 mg twice daily) or placebo in a crossover study design. After each 8-week period, subjects underwent at rest and adenosine-stress first-pass myocardial perfusion cardiovascular magnetic resonance, pulse-wave analysis, and endothelial function measurements using radial artery tonometry, blood sampling, anthropomorphic measurements, and quality-of-life assessment. Although no difference was found in global myocardial perfusion after TU compared with placebo, myocardium supplied by unobstructed coronary arteries showed increased perfusion (1.83 +/- 0.9 vs 1.52 +/- 0.65; p = 0.037). TU decreased basal radial and aortic augmentation indexes (p = 0.03 and p = 0.02, respectively), indicating decreased arterial stiffness, but there was no effect on endothelial function. TU significantly decreased high-density lipoprotein cholesterol and increased hip circumference, but had no effect on hemostatic factors, quality of life, and angina symptoms. In conclusion, oral TU had selective and modest enhancing effects on perfusion in myocardium supplied by unobstructed coronary arteries, in line with previous intracoronary findings. The TU-related decrease in basal arterial stiffness may partly explain previously shown effects of exogenous testosterone on signs of exercise-induced myocardial ischemia.

Comparison of flow characteristics and vascular reactivity of radial artery and long saphenous vein grafts [NCT00139399].

BACKGROUND: The morphological and functional differences between arteries and veins may have implications on coronary artery bypass graft (CABG) survival. Although subjective differences have been observed between radial artery (RA) and long saphenous venous (LSV) grafts, these have not been quantified. This study assessed and compared the flow characteristics and in-vivo graft flow responses of RA and LSV aorto-coronary grafts. METHODS: Angiograms from 52 males taken 3.7 +/- 1.0 months after CABG surgery were analyzed using adjusted Thrombolysis in Myocardial Infarction (TIMI) frame count. Graft and target coronary artery dimensions were measured using quantitative coronary angiography. Estimated TIMI velocity (V(E)) and volume flow (F(E)) were then calculated. A further 7 patients underwent in-vivo graft flow responses assessments to adenosine, acetylcholine and isosorbide dinitrate (ISDN) using intravascular Doppler. RESULTS: The V(E) for RA grafts was significantly greater than LSV grafts (P = 0.002), however there was no difference in volume F(E) (P = 0.20). RA grafts showed positive endothelium-dependent and -independent vasodilatation, and LSV grafts showed no statistically significant response to adenosine and acetylcholine. There was no difference in flow velocity or volume responses. Seven RA grafts (11%) had compromised patency (4 (6%) > or = 50% stenosis in the proximal/distal anastomoses, and 3 (5%) diffuse narrowing). Thirty-seven (95%) LSV grafts achieved perfect patency and 2 (5%) were occluded. CONCLUSION: The flow characteristics and flow responses of the RA graft suggest that it is a more physiological conduit than the LSV graft. The clinical relevance of the balance between imperfect patency versus the more physiological vascular function in the RA graft may be revealed by the 5-year angiographic follow-up of this trial.

Incidence, risk factors, and outcomes of catheter-related thrombosis in adult patients with cancer.

PURPOSE: Thrombosis of long-term central venous catheters (CVC) is a serious complication that causes morbidity and interrupts the infusion of chemotherapy, intravenous medication, and blood products. We performed a prospective study to examine the incidence, risk factors, and long-term complications of symptomatic catheter-related thrombosis (CRT) in adults with cancer. PATIENTS AND METHODS: Consecutive patients with cancer, undergoing insertion of a CVC, were enrolled and prospectively followed while their catheter remained in place plus 4 subsequent weeks or a maximum of 52 weeks, whichever came first. Patients with symptomatic CRT were followed for an additional 52 weeks from the date of CRT diagnosis. The end points were symptomatic CRT, symptomatic pulmonary embolism (PE), postphlebitic syndrome, and catheter life span. RESULTS: Over 76,713 patient-days of follow-up, 19 of 444 patients (4.3%) had symptomatic CRT in 19 of 500 catheters (0.3 per 1,000 catheter-days). The median time to CRT was 30 days and the median catheter life span was 88 days. Significant baseline risk factors for CRT were: more than one insertion attempt (odds ratio [OR] = 5.5; 95% CI, 1.2 to 24.6; P = .03); ovarian cancer (OR = 4.8; 95% CI, 1.5 to 15.1; P = .01); and previous CVC insertion (OR = 3.8; 95% CI, 1.4 to 10.4; P = .01). Nine of the 19 CRT patients were treated with anticoagulants alone, eight patients were treated with anticoagulants and catheter removal, while two patients did not receive anticoagulation. None had recurrent CRT or symptomatic PE. Postphlebitic symptoms were infrequent. CONCLUSION: In adults with cancer, the incidence of symptomatic CRT is low and long-term complications are uncommon.