Invited commentary.
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Heart-Assist Devices↗
Biomedical subjects
Stephen Large
Publications and source records attributed to Stephen Large.
Dose-related efficacy of aspirin after coronary surgery in patients With Pl(A2) polymorphism (NCT00262275).
BACKGROUND: To evaluate the impact of the genetic polymorphisms affecting aspirin response using platelet aggregation and the response to different aspirin doses after cardiopulmonary bypass, we performed a subanalysis of the results from a randomized trial evaluating low- and medium-dose aspirin and clopidogrel. METHODS: Blood was collected from consenting patients and DNA extracted. Polymerase chain reaction and restriction fragment length polymorphism analysis was performed to detect Pl(A2), C807T, and A842/C50T polymorphisms. Aspirin efficacy was assessed using light transmission platelet aggregometry, and reported as percentage aggregation and EC50 concentrations using the technique of Born. RESULTS: Of 90 patients, 80 consented to further genetic testing, of whom 63 patients were randomly assigned to medium- (325 mg) or low-dose (100 mg) aspirin. The Pl(A2), C807T, and A842/C50T gene frequencies were 30%, 66%, and 21%, respectively, with no identifiable differences in the baseline platelet aggregation. Postoperatively, after 5 days of aspirin, platelet aggregation was consistently but not significantly impaired with Pl(A2) and A842/C50T carriers and consistently but not significantly improved with C50T carriers. An interaction term was identified on percentage aggregation and EC50 using epinephrine. The interaction coefficient describes a higher aggregation of 19% (95% confidence interval: 2 to 36; p = 0.03) and less inhibition with an EC50 of -2.07 (-4.19 to 0.04; p = 0.06) in patients who were both Pl(A2) positive and receiving low-dose aspirin. CONCLUSIONS: Genetic polymorphisms that affect the response to aspirin are common. The impaired response of persons with the Pl(A2) polymorphism to aspirin may be dose related, with significant improvement observed in patients using medium- rather than low-dose aspirin.
Aged↗
Psychosocial issues for patients with ventricular assist devices: a qualitative pilot study.
BACKGROUND: Surgical implantation of a ventricular assist device is being used increasingly in patients in the United Kingdom, yet few studies have focused on patients' experiences from a phenomenological (psychological) perspective. OBJECTIVE: To explore, through a pilot study, the impact of implantation of a ventricular assist device on patients' bodies and lives. METHODS: This qualitative retrospective study included 6 patients (4 men and 2 women) and 3 of these patients' relatives. Patients were from 17 to 50 years old and had used Thoratec, Heartmate, or VentrAssist devices. RESULTS: The participants' accounts clustered around a number of themes, 2 of which are reported here: (1) body and self and (2) trust. Each theme comprised several subthemes: body and self had sub-themes of shock, restrictions, scarring, and infection; trust had subthemes of keeping me alive, device failure, and confidence. CONCLUSIONS: The ventricular assist device has a considerable effect on a patient's body and sense of self. This effect is often accommodated without much difficulty, but some patients and their families need additional psychological support during and after use of a ventricular assist device. Assessment before implantation of such a device can sometimes reveal this need, but such assessment may not be possible in emergency procedures. Trusting the new heart or the native recovered heart may be difficult for some patients. Further research is needed to understand this phenomenon.
Adaptation, Psychological↗
Biological efficacy of low versus medium dose aspirin after coronary surgery: results from a randomized trial [NCT00262275].
BACKGROUND: The beneficial effect of aspirin after coronary surgery is established; however, a recent study reported the inability of low doses (100 mg) to inhibit postoperative platelet function. We conducted a double-blind randomised trial to establish the efficacy of low dose aspirin and to compare it against medium dose aspirin. METHODS: Patients undergoing coronary surgery were invited to participate and consenting patients were randomised to 100 mg or 325 mg of aspirin daily for 5 days. Our primary outcome was the difference in platelet aggregation (day 5 - baseline) using 1 microg/ml of collagen. Secondary outcomes were differences in EC50 of collagen, ADP and epinephrine (assessed using the technique of Born). RESULTS: From September 2002 to April 2004, 72 patients were randomised; 3 patients discontinued, leaving 35 and 34 in the low and medium dose aspirin arms respectively. The mean aggregation (using 1.1 microg/ml of collagen) was reduced in both the medium and low dose aspirin arms by 37% and 36% respectively. The baseline adjusted difference (low - medium) was 6% (95% CI -3 to 14; p = 0.19). The directions of the results for the differences in EC50 (low - medium) were consistent for collagen, ADP and epinephrine at -0.07 (-0.53 to 0.40), -0.08 (-0.28 to 0.11) and -4.41 (-10.56 to 1.72) respectively, but none were statistically significant. CONCLUSION: Contrary to recent findings, low dose aspirin is effective and medium dose aspirin did not prove superior for inhibiting platelet aggregation after coronary surgery.
Adenosine Diphosphate↗
Invited commentary.
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Aortic Valve Stenosis↗
Biological efficacy of low against medium dose aspirin regimen after coronary surgery: analysis of platelet function.
The failure of aspirin to inhibit platelet function has been documented in patients undergoing coronary artery bypass graft (CABG) surgery, but the causes of "aspirin-resistance" remain uncertain. The aim of this study was to investigate the efficacy of aspirin in patients undergoing CABG surgery receiving either 100 mg or 325 mg of oral aspirin for 5-days. Platelet function was tested the day before surgery and on day +1 and day +5, and evaluated by changes in collagen-induced thromboxane-A2 (TxA2) release and platelet aggregation following stimulation with collagen, ADP and epinephrine. In all patients, baseline platelet aggregation was significantly inhibited by pre-incubation with in vitro aspirin (150 micromol/l), with a mean reduction in TxA2-release of >or=95.5% (82.3,99.1). After 5-days of oral aspirin, platelet aggregation was significantly inhibited, and was not further inhibited by in vitro aspirin. Oral aspirin was also associated with a >or=99.5% (97.8, 99.7) reduction in TxA2-release, and with the reversal of the second-phase of ADP-induced aggregation which is TxA2-dependent. In addition a single-dose of 325 mg aspirin on the first post-operative morning may have a greater inhibitory effect on collagen-induced aggregation than 100 mg aspirin. Western blot analysis provided no evidence for the presence of COX-2 in platelets, while the up-regulation of p38-MAPK following platelet-stimulation and surgery was seen. The inhibition of COX-2 (NS398) or p38-MAPK (SB203580) activity did not affect platelet aggregation and TxA2-release on day +5. In summary, there was no evidence for inherent or acquired aspirin-resistance in this surgical population, or for the involvement of either COX-2 or p38-MAPK.
Adenosine Diphosphate↗
What is the true (unbiased) percentage freedom from atrial fibrillation at 6 months after the modified Cox maze procedure using bipolar radiofrequency energy?
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Atrial Fibrillation↗
Clopidogrel did not inhibit platelet function early after coronary bypass surgery: A prospective randomized trial.
OBJECTIVE: Although the beneficial effect of aspirin prescription after coronary surgery has been established, the efficacy of clopidogrel has never been compared with that of aspirin in the critical early postoperative period. We therefore conducted a prospective, double-blind, randomized controlled trial to compare the efficacies of these antiplatelet regimens. METHODS: Patients undergoing elective primary coronary artery bypass surgery were invited to participate. After the operation, patients were randomized to receive 100 mg aspirin, 325 mg aspirin, or 75 mg clopidogrel tablets daily for 5 days. Our primary outcome measure was platelet aggregation on day 5, expressed as percentage of baseline. Assessment of platelet aggregation was undertaken with the technique of Born. RESULTS: From September 2002 to July 2003, a total of 54 patients were randomized into the study. There were 2 self-withdrawals and 2 protocol violations, leaving 50 patients for analysis, 34 in the aspirin group and 16 in the clopidogrel arm. Compared with baseline, the mean percentage aggregations with collagen on day 5 were 56% for aspirin and 99% for clopidogrel. The mean difference between the two arms was 42% (95% confidence interval 27%-56%) in favor of aspirin. At the same time point, the effective concentration to inhibit 50% aggregation in the samples from patients randomly assigned to receive clopidogrel were not raised for our entire panel of agonists (changes of -0.04 microg/L for collagen, -0.01 micromol/L for epinephrine, and -0.02 micromol/L for adenosine diphosphate). CONCLUSION: Clopidogrel, unlike aspirin, did not inhibit platelet aggregation in the first 5 postoperative days and therefore should not be used as a sole antiplatelet agent early after coronary surgery.
Aged↗
Immunosuppression, eotaxin and the diagnostic changes in eosinophils that precede early acute heart allograft rejection.
Peripheral blood eosinophil counts (EOS) are undetectable in 40% blood samples sent for routine haematology at Papworth Hospital during the first 3 months after heart transplantation (HTx). Increases in EOS usually precede the development of allograft rejection by a median of 4 days. We compared the effects of cyclosporin (dose and total blood concentration), prednisolone (dose and both total and unbound plasma concentrations) and azathioprine, as well as plasma concentrations of the CCR-3 chemokines, eotaxin and RANTES, on changes in EOS in 47 consecutive HTx recipients, with a median follow-up of 90 (IQR 85-95) days. Multivariate analysis confirmed the independent association between both prednisolone dose (P<0.0001) and eotaxin (P<0.0001) and changes in EOS. The plasma eotaxin concentration was, in turn, most closely associated with the cyclosporin dose (P<0.001) and plasma prednisolone concentration (P=0.022). The blood cyclosporin concentration (P=0.028), EOS (P=0.012) and prednisolone dose (P=0.015) were all independently associated with the risk of treated acute rejection. When prednisolone pharmacokinetic parameters were substituted for the prednisolone dose in this multivariate model, only the pharmacokinetic parameter retained a significant association with the risk of rejection. Changes in EOS preceding cardiac allograft rejection are directly associated with plasma eotaxin concentrations and indirectly with prednisolone dosage. Cyclosporin may also indirectly influence these changes by inhibiting eotaxin production. EOS, prednisolone dose and blood cyclosporin concentrations were independently associated with the risk of acute rejection. The total and unbound fractions of prednisolone in plasma appear to be even more closely related to rejection but are difficult to measure. Monitoring EOS, as a surrogate measure of prednisolone immunosuppression, may be more cost-effective for controlling rejection than conventional cyclosporin monitoring in the first 6 weeks after HTx.
Chemokine CCL11↗
A versatile technique for aortic root replacement without pre-manufactured composite graft: a 12-year experience.
BACKGROUND AND AIM OF THE STUDY: Replacement of the aortic root is the treatment of choice for aneurysmal dilatation. Many modifications of the Bentall technique have been described, as have valve-sparing procedures. The study aim was to determine the outcome of a versatile modification of composite replacement that has been adopted over the past 12 years. Separate graft and prosthetic valve components were used to allow freedom of valve choice and the use of an appropriately sized graft for the distal aortic anastomosis. METHODS: Between January 1990 and March 2002, 59 patients (45 males, 14 females; mean age 56 +/- 14 years) underwent aortic root replacement using this technique. Indications for surgery were elective in 35 patients and emergent (usually type A aortic dissection) in 24. The range of valve prostheses used, their size, and the size of aortic graft used in each case was assessed. Durations of ischemia and cardiopulmonary bypass were recorded, as was postoperative blood loss and subsequent patient progress, including valve-related events, perioperative mortality and actuarial survival. RESULTS: A wide range of aortic graft sizes was combined with both mechanical and tissue valves (from 1-7 mm larger in diameter). Median postoperative blood loss was 550 ml (IQR 400-800 ml). Perioperative mortality was 5.1%. There were no valve- or technique-related deaths, and the median actuarial survival was 13.17 years. During a 12-year follow up there were no proximal aortic reoperations. CONCLUSIONS: This technique had favorable perioperative mortality, produced a secure proximal suture line, and allowed the surgeon free choice of both valve type and size of aortic graft. This minimized tension at the distal suture line, and produced good hemostasis, especially in those patients with fragile dissected tissues.
Adult↗
Indirect comparison meta-analysis of aspirin therapy after coronary surgery.
OBJECTIVES: To evaluate the efficacy of low and medium dose aspirin therapy after coronary surgery by using an indirect comparison meta-analysis. DATA SOURCES: Systematic literature search of Medline, Embase, Cochrane controlled trials register, and trial register sites on the internet. STUDY SELECTION: Outcome was evaluated by angiography and reported as graft occlusion and rate of events in patients. Trials that did not include aspirin as the sole therapy or did not have a placebo control arm were excluded. Articles were assessed for eligibility and quality and grouped according to dosage. The estimated difference in effect of low and medium dose aspirin on graft occlusion was obtained by combining the estimated log relative risks of low dose with placebo and medium dose with placebo. RESULTS: For graft occlusion, the medium dose trials yielded a relative risk reduction of 45% compared with 26% for the low dose trials. The greater effect in the medium dose trials is summarised by a relative risk ratio of 0.74 (95% confidence interval 0.52 to 1.06; P = 0.10) for graft occlusion and 0.81 (0.57 to 1.16; P = 0.25) for events in patients. CONCLUSIONS: Medium dose aspirin may more successfully reduce graft occlusion than low dose regimens within the first year after coronary surgery.
Aspirin↗
Short- and long-term outcomes of combined cardiac and renal transplantation with allografts from a single donor.
Coexisting end-stage heart and kidney failure can be treated by combined cardiac and renal transplantation. This study reviews the short- and long-term outcomes after such a procedure over a 16-year period at a single institution. All patients who underwent single-donor simultaneous heart and kidney transplantation during the period of March 1986 to April 2002 (including heart retransplantation) were included (n = 13). They were listed for combined heart and kidney transplantation as they fulfilled our criteria for irreversible end-stage organ failure. Retrospective review of patient data from the transplant database, patient case notes and post-mortem reports were carried out. The mean (SD) recipient age was 45 (12) years and there were 2 females. The mean pre-operative creatinine level was 724 (415) micromol/liter with 9 patients (69.2%) on continuous ambulatory peritoneal dialysis and 2 patients (15.4%) on hemodialysis prior to transplantation. The 30-day mortality rate was 15.4% (2 of 13). For surviving patients the mean creatinine level at hospital discharge was 158 (93) micromol/liter. The mean number of acute cardiac rejection episodes per 100 patient-days was significantly lower (p = 0.01) than that for the heart-only transplant group (n = 760) during the same period. The median (interquartile range) post-operative survival was 1,969 (620 to 3,468) days. The actuarial survival rates (95% confidence interval) at 1 and 10 years were 77% (54% to 100%) and 67% (40% to 94%), respectively, and were not significantly different from the isolated heart transplant population (p = 0.68). Only 1 episode of acute renal rejection was diagnosed on clinical grounds, which was treated accordingly. There was no renal allograft loss in the long-term survivors. Combined cardiac and renal transplantation with allografts from the same donor has acceptable short- and long-term outcomes for patients with coexisting end-stage cardiac and renal failure. This group of patients may also experience fewer acute rejection episodes post-operatively.
Adult↗