Paramedic-led prehospital thrombolysis is safe and effective: the East Anglian experience.

INTRODUCTION: Prehospital thrombolysis has been shown to improve patient outcomes in clinical trials and this has been confirmed in the ongoing large national myocardial infarction registry (Myocardial Infarction National Audit Project; MINAP) reports. This paper describes a system to improve the delivery of prehospital thrombolysis and the associated governance requirements to gain maximum patient benefit. METHODS: Demographic data were prospectively collected on all patients treated by the East Anglian Ambulance Trust with bolus thrombolytics for a presumed diagnosis of ST elevation myocardial infarction between November 2003 and February 2007. Survival status was determined from the NHS strategic tracing service. RESULTS: 1062 patients (mean age 64.0 years (SD 10.6), 795 men) were treated in this time period. There were 71 deaths in this group, with actuarial survival of 93.9% (SE 0.9%) at 30 days, 91.7% (SE 1.0%) at 6 months and 90.8% (SE 1.1%) at 12 months after treatment. Age and cardiac arrest were most strongly associated with mortality (both p<0.001). Twelve (1.2%) patients received thrombolysis that on review was considered inappropriate. There were no deaths in this subgroup. CONCLUSIONS: Prehospital thrombolysis can be administered safely by ambulance staff supported by a Trust clinical support system with excellent clinical outcomes.

Clinical and cost-effectiveness analysis of an open label, single-centre, randomised trial of spinal cord stimulation (SCS) versus percutaneous myocardial laser revascularisation (PMR) in patients with refractory angina pectoris: The SPiRiT trial.

BACKGROUND: Patients with refractory angina have significant morbidity. This study aimed to compare two of the treatment options, Spinal Cord Stimulation (SCS) and Percutaneous Myocardial Laser Revascularisation (PMR) in terms of clinical outcomes and cost-effectiveness. METHODS: Eligible patients were randomised to PMR or SCS and followed up for exercise tolerance time (ETT), Canadian Cardiovascular Society (CCS) classification and the quality of life measures SF-36, Seattle Angina Questionnaire and the EuroQoL at 3, 12 and 24 months. Utilities were calculated using the EQ-5D and these and costs were compared between groups. The incremental cost-effectiveness ratio (ICER) per QALY for SCS compared to PMR was also calculated. RESULTS: At 24 months post-randomisation, patients that had SCS and PMR had similar ETT (mean difference 0.05, 95% CI -2.08, 2.18, p = 0.96) and there was no difference in CCS classification or quality of life outcomes. The difference in overall mean costs when comparing SCS to PMR was GBP5,520 (95% CI GBP1,966 to GBP8,613; p < 0.01) and the ICER of using SCS was GBP46,000 per QALY. CONCLUSION: Outcomes after SCS did not differ appreciably from those after PMR, with the former procedure being less cost-effective as currently applied. Larger studies could clarify which patients would most benefit from SCS, potentially increasing cost-effectiveness. TRIAL REGISTRATION: Current Controlled Trials ISRCTN09648950.

Influence of thrombolytic therapy on the patterns of ventricular septal rupture after acute myocardial infarction.

BACKGROUND: Post-myocardial infarction ventricular septal defect (VSD) complicates approximately 2% of myocardial infarctions. Thrombolytic therapy may accelerate the time from myocardial infarction to VSD formation. The effects of thrombolytic therapy in patients with a post-myocardial infarction VSD were investigated. METHOD: Demographic, procedural, and event data were retrospectively analysed in patients transferred to a regional cardiothoracic centre with the diagnosis of post-myocardial infarction VSD over five years. RESULTS: Twenty nine patients were analysed; 15 received thrombolytic therapy: 10 (<12 hours) early and five (> or =12 hours) late. The median time to post-myocardial infarction VSD was shorter with thrombolytic therapy at 1 v 5.5 days (p=0.01). The median time to post-myocardial infarction VSD was shorter with early compared with late thrombolytic therapy at 1 v 6 days (p<0.01). There was no difference between late and no thrombolytic therapy, 5.5 v 6 days. Patients treated with thrombolytic therapy had a trend towards higher mortality at 11/15 (73%) compared with 5/14 (36%) (p=0.066). Twenty five (86%) patients had surgery. All four not having surgery died. Surgical survival was 13/25 (52%) at discharge and six months of follow up. Within the surgical group survival with prior thrombolytic therapy was 4/25 (25%) and 9/13 (69%) without (p=0.07). CONCLUSION: There appears to be an earlier presentation of post-myocardial infarction VSD when thrombolytic therapy has been used. An early presentation can carry a worse prognosis and may have implications for the identification and treatment of this life threatening complication.

A UK trial-based cost--utility analysis of transmyocardial laser revascularization compared to continued medical therapy for treatment of refractory angina pectoris.

OBJECTIVE: Transmyocardial laser revascularization (TMLR) is used to treat patients with refractory angina considered unsuitable for conventional forms of revascularization. Using patient specific data from a single centre UK randomised-controlled trial, we aimed to determine whether, from a UK National Health Service (NHS) perspective, TMLR plus standard medical management is cost-effective when compared with standard medical management alone. METHODS: One hundred and eighty-eight patients assessed as having refractory angina, and not suitable for conventional forms of revascularization were randomized to receive TMLR and medical management (94) or medical management alone (94). Costs to the UK NHS of TMLR (where appropriate), and all secondary sector health care contacts and cardiac-related medication in the 12 months following randomization, were collected. Patient utility as measured using the EuroQol EQ-5D questionnaire was combined with 12-month survival data to generate quality adjusted life years (QALYs). RESULTS: The mean cost per patient over the year from hospitalization for TMLR was 11,470 pounds sterling and for medical management alone was 2586 pounds sterling, giving a cost difference of 8901 pounds sterling (95% confidence interval (CI) 7502 pounds sterling--10,008 pounds sterling: P < 0.0001). The mean QALY difference, in favour of TMLR was 0.039 (95% CI -0.033 to 0.113: P = 0.268). This gives an incremental cost per QALY of over 228,000 pounds sterling. Analysis of stochastic uncertainty and of sensitivity to gross changes in key parameters consistently produces very high costs per QALY. CONCLUSIONS: The policy implications are clear: for such patients TMLR is an inefficient use of UK health service resources. This conclusion would not be changed by considerable improvements in effectiveness or reductions in cost.

Quantitative analysis of myocardial perfusion changes with transmyocardial laser revascularization.

Transmyocardial laser revascularization (TLR) is a technique of creating left ventricular transmural channels in patients with refractory angina. We aimed to measure perfusion changes quantitatively using technetium-99m methoxyisobutyl isonitrile. Perfusion scans were performed on 94 TLRs and in 94 control patients at rest and during exercise at assessment, and 3-, 6-, and 12-month follow-up. A serial set of scans allowed direct comparison of each patient over all visits. Bull's-eyes were divided into 5 anatomic regions and a 20-region model. Severity values were calculated for rest, stress, and each cardiac region using a threshold of 1 for analysis. Higher scores indicated greater severity of ischemia and lower perfusion. At 3-month follow-up, the severity was significantly worse during TLR than in control patients both during stress (0.172 +/- 0.003 and 0.161 +/- 0.003, respectively, p = 0.007) and at rest (0.170 +/- 0.003 and 0.158 +/- 0.003, respectively, p = 0.002). At 6 months, severity during stress was 0.176 +/- 0.003 with TLR and 0.162 +/- 0.003 in controls (p = 0.001), with no significant difference at rest. At 12 months, there was no significant difference between TLR and control groups at stress and rest. Regional severity deteriorates during TLR compared with control patients anteriorly (p = 0.001, p = 0.0016, p = 0.005 at 3, 6, and 12 months), apically (p = 0.005, p = 0.0046, p = 0.032, respectively), and laterally (p <0.0001, p = 0.001, p = 0.002, respectively). An apparent improvement is observed in the inferoseptal region at 6- and 12-month follow-up-an area not lasered. Thus, TLR appears to produce deterioration in resting myocardial perfusion in lasered regions, and improvement in nonlasered regions, with no difference in exercise-induced myocardial ischemia compared with that in control patients.

Tamoxifen effects on endothelial function and cardiovascular risk factors in men with advanced atherosclerosis.

BACKGROUND: Tamoxifen and its analogues act as selective estrogen receptor modulators (SERMs) in women, with estrogen-like activities on some plasma cardiovascular risk factors (eg, lipoproteins). Effects of SERMs on men with coronary artery disease (CAD) have not been reported. METHODS AND RESULTS: Thirty-one men with angiographically proven CAD were recruited; 16 were treated with tamoxifen (40 mg/d) for 56 days, and 15 were untreated. All the CAD patients were medicated with aspirin and an HMG-CoA reductase inhibitor for >/=6 weeks before entering the study. Ten men with angina-like symptoms but normal coronary arteries by angiography (NCA group) were also treated with tamoxifen. Blood samples were collected at days -7, 0, 7, 14, 21, 28, and 56 of treatment. Endothelium-dependent flow-mediated dilatation (ED-FMD) of the brachial artery was measured by high-resolution ultrasound at 5 visits. Tamoxifen caused an increase in %ED-FMD maximal at 28 days in the CAD group (2.1+/-0.3% to 7.5+/-0.7%; P<0.0001) and the NCA group (3.8+/-0.4% to 7.9+/-1.0%; P<0.0001), with no significant change in the untreated group. Tamoxifen also caused decreases in several plasma cardiovascular risk factors, including total cholesterol, triglycerides, lipoprotein(a), and fibrinogen. Except for the triglyceride response, these effects were similar to those reported for postmenopausal women treated with tamoxifen. CONCLUSIONS: Tamoxifen substantially increased ED-FMD in men with CAD who were taking conventional medication. Together with the effects on risk factors, the data strongly support clinical evaluation of SERMs for the treatment of men with CAD.

Laser revascularization in the management of coronary artery disease.

In recent years, laser therapy has been evaluated for the treatment of patients with angina who have coronary artery disease which is not amenable to conventional revascularization techniques. The results of transmyocardial revascularization and percutaneous myocardial revascularization are reviewed.

Laser revascularisation.

Patients who present with angina pectoris due to underlying coronary artery disease which is not controlled by medical therapy, and who have disease which is not amenable to conventional forms of revascularisation, present an increasing clinical problem. Laser techniques have been introduced to improve myocardial perfusion in this group of patients. The surgical technique of transmyocardial laser revascularisation has been evaluated in this patient population. Generally, there has been a good symptomatic response in terms of improvement in angina, and in some studies an increase in exercise capacity. The technique, however, does carry significant morbidity and mortality. More recently, a catheter-based technique has been introduced--percutaneous myocardial laser revascularisation. This technique seems to improve symptoms of angina, produce an increase in exercise capacity, with a much more favourable procedural risk profile.

Bacterial endocarditis following repeated tattooing.

Body decoration in the form of tattooing is becoming increasingly popular, especially among younger age groups. Although serious infections following tattooing are rare they are well documented. The first reported case of endocarditis caused by repeated tattooing in an individual with known valvar heart disease is presented.

Coronary angiography in the presence of peripheral vascular disease: femoral or brachial/radial approach?

Peripheral vascular disease is considered a relative contraindication to the femoral approach for coronary angiography, but no data exist comparing the femoral and brachial/radial routes under these circumstances. We examined the influence of vascular approach on outcome. Two hundred and ninety-seven patients, mean age 67.1 +/- 8.4 years, with clinical or radiographic evidence of aortofemoral peripheral arterial disease underwent diagnostic coronary angiography during a 3-year period at this cardiothoracic center. The approach was successful in 121 of 154 femoral cases (79%) compared with 130 of 143 brachial/radial cases (91%; P < 0.01). Of the 33 failed femoral cases, 15 were then approached from the other femoral artery, with success in 6 (40%), while 18 were approached from the arm, with success in all (100%; P < 0.01). Brachial/radial cases took significantly longer than femoral cases (51 +/- 19 vs. 42 +/- 22 mins; P < 0.01). In cases where the femoral pulse was considered normal, the femoral approach nonetheless failed in 19 of 95 (20%). Major vascular complications (e.g., pulseless limb, arterial dissection, hemorrhage, or false aneurysm) occurred in nine femoral cases vs. zero brachial/radial cases (P < 0.01). Patients with peripheral vascular disease who undergo coronary angiography from the femoral artery have a 1-in-5 risk of procedural failure, necessitating use of an alternative vascular approach, and a 1-in-20 risk of a major vascular complication. Normality of femoral arterial pulsation is not a good predictor of femoral success. Brachial/radial approaches take longer, but succeed more frequently and have a negligible major vascular complication rate. We believe that patients with peripheral vascular disease should undergo coronary angiography via brachial or radial approach. Cathet. Cardiovasc. Intervent. 49:32-37, 2000.

Measurement of myocardial blood flow with positron emission tomography before and after transmyocardial laser revascularization.

BACKGROUND: Transmyocardial laser revascularization (TMLR) has been proposed for treatment of refractory angina. It has been hypothesized that transmural left ventricular channels created by laser improve myocardial blood flow (MBF) in the treated zones. We aimed to assess the effect of TMLR on MBF and coronary vasodilator reserve (CVR). METHODS AND RESULTS: We measured MBF by means of PET with (15)O-labeled water in 7 patients with refractory angina, Canadian Cardiovascular Society (CCS) class 3.6+/-0.5, on 3 occasions: before and at 7.5+/-2.8 weeks (FU-1) and 34.6+/-4.7 weeks (FU-2) after TMLR performed with a synchronized, high-powered CO(2) laser. In each study, MBF was measured at rest and during maximal intravenous dobutamine. CVR was computed as dobutamine divided by resting MBF. After TMLR, CCS class was 2.2+/-1.7 at FU-1 and 2.4+/-1 at FU-2 (P=0.04 versus pre-TMLR). Resting MBF in both lasered and nonlasered regions was unchanged after TMLR. Dobutamine MBF at baseline was 1.45+/-0.52 and 1.55+/-0.52 mL. min(-1). g(-1) in lasered and nonlasered regions, respectively (P=NS). At FU-1, dobutamine MBF in nonlasered regions had increased significantly to 1.89+/-0.82 mL x min(-1) x g(-1) (P<0.05) and was higher than in lasered regions (1.51+/-0.61 mL x min(-1) x g(-1); P<0.05 versus nonlasered). At FU-2, dobutamine MBF in nonlasered regions was still higher than in lasered regions (1.56+/-0.54 versus 1.21+/-0.44 mL x min(-1) x g(-1); P<0.01). CVR was comparable in nonlasered and lasered regions at baseline and FU-1, whereas it was higher in nonlasered regions at FU-2 (1.86+/-0.67 versus 1.53+/-0.72 mL x min(-1) x g(-1); P<0.05). CONCLUSIONS: TMLR has been shown to reduce angina in severely diseased patients. The results of our study do not support the hypothesis that the symptomatic benefit of TMLR can be ascribed to improved myocardial perfusion or CVR in lasered areas.

The utility of pacemaker evoked T wave amplitude for the noninvasive diagnosis of cardiac allograft rejection.

Previous work suggested that pacemaker evoked T wave amplitude (ETWA) may be a sensitive noninvasive marker of cardiac allograft rejection. A Topaz QT sensing rate responsive pacemaker (Vitatron Medical) was implanted at transplantation using epicardial ventricular leads in 45 recipients (35 males; median age 51 years, range 20-63). The median duration of follow-up was 129 days (range 4-327). The ETWA at a paced rate of 100 beats/min was measured daily during hospitalization and at each outpatient attendance (900 readings). Endomyocardial biopsies were at routine intervals or when otherwise clinically indicated (257 biopsies with concurrent ETWA data). There were 58 episodes of rejection > or = grade 3a in 28 patients. The biopsies were classed as either no rejection (grade < 3a) or rejection requiring treatment (grade > or = 3a). The median normalized ETWA was 100.8% (range 24.6-239.7) without rejection and 89.9% (17.0-189.7) with rejection (Mann-Whitney U Test: P = 0.028). The performance of ETWA monitoring as a diagnostic test for the individual recipient was evaluated with exponentially weighted moving average quality control charts. For the diagnosis of all rejection episodes, ETWA monitoring had a sensitivity of 55%, a specificity of 62%, a positive predictive value of 30%, and negative predictive value of 83%. It is concluded that although analysis of pooled data showed a significant reduction in normalized ETWA with biopsy proven rejection, ETWA monitoring requires further refinement to improve sensitivity before it can be considered a clinically useful technique for the non-invasive diagnosis of cardiac allograft rejection in individual recipients.