Sex-related differences in eligibility for reperfusion therapy and in-hospital outcome after acute myocardial infarction

AIMS: To determine the effect of sex on reperfusion therapy and earlymortality after acute myocardial infarction. MEHTODS: We analysed the characteristics, the reperfusion interventions,and in-hospital mortality in 400 consecutive patients (320 menand 80 women) admitted during the first 6 h of acute myocardialinfarction and treated by primary angioplasty, or intravenousthrombolysis with rescue angioplasty. RESULTS: The differences between men and women were age (57 vs 67 years,P=0·001), systemic hypertension (33 vs 50%, P=0·02),cigarette smoking (79 vs 30%, P=0·0001) and contraindicationsto thrombolysis (28·5 vs 42·5%, P=0·02).Successful reperfusion of the infarct-related artery was achievedin 84% of patients of both sexes. In-hospital mortality was7·2% in men and 18·7% in women (P=0·001).Multivariate analysis was performed by linear logistic regressionin order to compare several embedded models, using repeatedmaximum likelihood ratio tests. The best model involved thevariables of cardiogenic shock and age. Addition of the variable‘sex’ did not improve the predictive power of thismodel (P<0·5). CONCLUSIONS: During acute myocardial infarction, similar successful earlyreperfusion rates can be achieved in men and women, despitethe lower eligibility of women for thrombolytic therapy. Althoughin-hospital mortality was higher in women than men, the bestpredictive model of mortality was the combination of age andcardiogenic shock. Therefore, sex does not appear to be an independentpredictor of mortality.     

The 60 Minutes Myocardial Infarction Project. Characteristics on admission and clinical outcome in patients with reinfarction compared to patients with a first infarction

Purpose The purpose of the study was to evaluate parameters that characterizepatients with myocardial reinfarction as compared to patientswith a first infarction in clinical practice, and possibly todetermine their clinical outcome. Methods The 60 Minutes Myocardial Infarction Project is a German multicentreprospective observational study in which 136 hospitals are participating.Fourteen thousand, nine hundred and eighty consecutive patientswith acute Q wave myocardial infarction were included from July1992 to September 1994. Results Out of these 14980 patients, there were 2854 (19%) with reinfarctionand 12126 (81%) with a first infarction. Patients with a reinfarctionarrived at the hospital 24min earlier than patients with a firstinfarction (pre-hospital delay 156 vs 180min;P<0·001);the door-to-needle time with reinfarction was longer (38 vs30min;P<0·001); however, patients with reinfarctionwere older (69 vs 66 years;P<0·001), had a lower rateof a diagnostic first ECG (54 vs 71%;P<0·001) andreceived thrombolytic therapy less frequently than patientswith a first infarction (46 vs 52%;P<0·001). A lownumber of patients received primary PTCA (n=205) since onlya few hospitals offered a primary PTCA service at the time thestudy was performed. In patients with reinfarction, there weremore reasons as to why thrombolytic therapy was not given (24vs 21%;P<0·001). Left bundle branch block occurredmore frequently in patients with reinfarction (15 vs 8%;P<0·001).The intra-hospital course in patients with reinfarction wasassociated with an increase of complications and intra-hospitaldeath (23 vs 15%;P<0·001). Conclusions Although reinfarction patients arrived earlier at hospital thanpatients with a first infarction, the former received thrombolytictherapy less frequently than the latter. Patients with reinfarctionwere older, more frequently had a non-diagnostic ECG on admissionand had a higher rate of contraindications against thrombolytictherapy.     

Impact of restenosis 10 years after coronary angioplasty

Aims The aim of the study was to compare the 10-year follow-up resultsof patients with or without restenosis following single-vesselpercutaneous transluminal coronary angioplasty (PTCA). Methods and Results A total of 313 patients with successful PTCA (20% reductionin luminal diameter narrowingwithout acute complications) anda control angiography 6 months after PTCA were included in thestudy. Events during the follow-up period were defined as death,myocardial infarction, bypass surgery, or repeat PTCA. Statisticalevaluation was performed by the Fisher test, logistic regression,and life-table analysis. Restenosis (loss of >50% of the initialgain and diameter stenosis of <50%) was found in 87 (28%)patients. During follow-up, 11 patients (5%) without restenosis(group A) and 11 (13%) patients with restenosis (group B) died(P<0·05). In group A, 17 (8%) patients and in groupB, 11 (13%) patients suffered myocardial infarction (ns); 17group A (8%) patients and 25 (29%) group B patients had bypasssurgery (P<0·0001), and 34 (15%) group A patientsand 55 (63%) group B patients underwent repeat PTCA (P<0·0001).Logistic regression analysis identified restenosis as an independentrisk factor that increases the risk of death 2·8-fold(P=0·02), bypass surgery 5·6-fold (P<0·0001),and repeat PTCA 10-fold (P<0·0001). Conclusion: We conclude that patients with restenosis had a poorer long-termoutcome than patients without restenosis. Although most patientswith restenosis underwent repeat PTCA, the survival rate withoutany serious adverse events was only 59%, compared with 83% inpatients without restenosis (P<0·0001).     

Pre-hospital thrombolytic therapy with either alteplase or streptokinase: Practical applications, complications and long-term results in 529 patients

OBJECTIVE: To assess the practical application, safety and long-term outcomeof pre-hospital thrombolytic intervention with either alteplaseor streptokinase in patients with extensive myocardial infarction. DESIGN: Prospective study. SUBJECTS: Patients with chest pain of more than 30 min duration, presentingwithin 6 h of symptom onset and with electrocardiographic evidenceof extensive evolving myocardial infarction. METHODS: Eligibility of patients was established by the general practitioneror the ambulance nurse using a standardized questionnaire with(contra-) indications for thrombolytic therapy. ComputerizedECG was recorded by ambulance nurses. In the presence of extensiveST segment elevation (sum ST deviation of at least 1·0m V), eligible patients received either 100 mg alteplase (n=246)or 50 mg alteplase in the ambulance followed by 0·75x 10⁶ IE streptokinase in hospital (n=90), or 1·5 x 10⁶IE streptokinase intravenously (n=193). MAIN OUTCOME MEASUREMENTS: Death and life-threatening complications (ventricular fibrillation,cardiac arrest) and side effects (hypotension, allergic reactions)during transportation to hospital and in the first 24 h followinghospitalization, and survival up to 5 years follow-up. RESULTS: From 1988–1993, 529 patients received thrombolytic treatmentinitiated pre-hospital. The time gained by pre-hospital administrationof thrombolysis amounted to 50 min. The rate of complicationsduring transportation and during the first 24 h after hospitalizationwas low. Hospital mortality was 2% and 1-year mortality 3%.Cumulative survival at 5 years was 92%. This was superior tothe 84% 5-year survival observed in a matched group of 239 patientswith similar baseline characteristics treated with alteplasein hospital. CONCLUSIONS: Pre-hospital administration of either alteplase or streptokinaseis feasible and safe and results in significant time gain. Thelong-term prognosis is excellent in spite of extensive evolvingmyocardial infarction upon admission.     

Risk stratification after myocardial infarction: A reappraisal in the era of thrombolysis

Objectives The present study was performed to evaluate whetherthe modalities of risk stratification after myocardial infarctionwere still operative in the thrombolytic era. Background Prediction of fatal events in the aftermath of myocardialinfarction relies on tests which aim to assess myocardial function,residual ischaemia and propensity for ventricular arrhythmias.Recent data on improved myocardial infarction prognosis haveled to the view that risk stratification needs to be updated. Methods In this multicentre, prospective study, 471 acute myocardialinfarction patients, 45% of whom were given thrombolytic therapy,were enrolled from the 10th day and underwent all or part ofthe following tests: exercise test, radionuclide ventriculography(resting and exertional ejection fraction), Holter monitoring,signal-averaged electrocardiography and programmed electricalstimulation. Univariate and multivariate analyses were performedto identify predictors of mortality. Results One year and long-term (mean follow-up 31·4 months)mortality rates were 5·5% and 8·4% respectively.Prediction of mortality was assessed and the role of the followingvariables was thus determined: age over 56 years (P=0·01),previous coronary attacks (P>0·001), history of heartfailure (P>0·001), early heart failure after myocardialinfarction (P=0·017), maximum workload of lest than 120W at exercise test (P=0·014), ineligibility to performexercise (P=0·002), depressed left ventricular ejectionfraction (P=0·013), late potentials as identified using50 Hz high pass filtering (P=0·012), mean night-timecycle length of less than 750 ms (P0·001), standard deviationof day time RR intervals of less than 100 ms (P=0·04),the last two measures reflecting heart rate variability. Inthis population, neither ventricular ectopic activity nor inducibilityof sustained monomorphic ventricular tachycardia at electrophysiologicalstudy carried any prognostic significance. Multivariate analysesshowed that decreased heart rate variability, presence of latepotentials and low ejection fraction (>30%) made an independentcontribution to the survival models. Conclusion In the current context of management of acute coronarypatients, the basis for risk stratification after myocardialinfarction remain roughly unchanged.     

The 60 Minutes Myocardial Infarction Project: Treatment and clinical outcome of patients with acute myocardial infarction in Germany

AIMS: To describe patient characteristics, pre-hospital delay, treatment,complications and outcome in patients with acute myocardialinfarction admitted to hospitals in Germany. METHODS AND RESULTS: The study was of prospective observational multicentre design.Those involved were consecutive patients with acute Q-wave myocardialinfarction admitted within 96 h of onset of symptoms to 136German hospitals between July 1992 and September 1994 (n=14980,median age 66 (quartiles 57, 74) years, 68% male, 48% anteriorwall infarction). Median pre-hospital delay was 170 (90, 475)min, with 17% arriving within the first hour and 61% within4 h of onset of symptoms. The following patient groups had ashort pre-hospital delay: males, those aged less than 65 years,those admitted at night or the weekend, those with a previousmyocardial infarction, those in need of cardiopulmonary resuscitation,and those with a diagnostic first ECG. The first ECG was diagnosticin 67·6% of cases. Reperfusion therapy was used in 53%,with thrombolytic therapy in 51·6%. Median time fromadmission to initiation of treatment was 30 (20, 55) min. Respectiverates of treatment with aspirin, nitrates, and beta-blockerswere 81%, 83% and 16%. Major complications were cerebral bleeding(0·4%), bleeding requiring transfusions (0·9%),left ventricular rupture (0·6%) and anaphylactic shock(0·1%). Median hospital stay was 20 (13, 26) days. In-hospitaldeath rate was 17·2%. Increased hospital mortality wasobserved with female gender, an unknown or long pre-hospitaldelay, a diagnostic first ECG, anterior wall infarction, traumaor major operation within the last 14 days, renal insufficiencyand malignoma. CONCLUSIONS: ‘Real-life’ hospital mortality is much higher thanpreviously reported in clinical trials. To reduce hospital mortality,the efficacy of thrombolysis should be increased by shorteningthe pre-hospital delay, and the use of concomitant therapy,especially beta-blockers, should be increased.     

Release of chemoattractants and neutrophil activation in acute myocardial infarction immediately after successful recanalization of the infarct-related vessel by angioplasty

The study investigated inflamatory responses in evolving myocardialinfarction. Fifteen patients with acute myocardial infarction,who had undergone balloon recanalization of the infarct-relatedcoronary artery within 4 h after onset of symptoms, were examined.Blood samples were obtained through the guiding catheter andfrom the pulmonary artery before and immediately after successfulrecanalization. After recanalization, plas from the pulmonaryartery was 47% (quartiles: l9%, 78; P =0·001) more chemotacticto neutrophils from normal donors than before recanalization.Furthermore, significant changes in neutrophil function werefound in the pulmonary artery. Compared to the values beforerecanalization, the nitroblue tetrazolium score rose by 31%(quartiles: 4%, 37% P=0·003), FMLP-stimulated superoxideanion production by 10% (quartiles: 0%, 39% P=0·020),and chemotaxis by 46% (quartiles: 0%, 81%, P=0·011),while neutrophil filterability decreased by 28% (quartiles:15%, 47%; P=0·010). No significant changes in neutrophilparameters were found in the arterial blood The study indicatesthat chemoattractants are released in the early reperfusionperiod of evolving myocardial infarction. These chemoattractantsmay act as inflammatory mediators causing neutrophil activation.     

Comparison of two methods of determining renal perfusion with and without captopril pretreatment in groups of patients with left ventricular dysfunction

Methods of effective renal plasma flow measurement by ¹²⁵I-orthoiodohippurateelimination and para-aminohippurate clearance were comparedwith and without captopril pretreatment in 10 chronic heartfailure patients and in 20 patients after transmural myocardialinfarction. In the chronic heart failure group measurements of effectiverenal plasma flow by the two techniques were strongly correlated(r=0·92, P<0·00001), as was the captopril-mediatedchange in effective renal plasma flow by the two methods (r=0·85,P=0·002). However, in absolute terms para-aminohippurateclearance significantly exceeded ¹²⁵I-orthoiodohippurate clearanceby a mean (± SD) of 24·8 ± 43·7ml. min^–1 (P<0·05) so that only using the formertechnique was a signifincant in renal perfusion observed inresponse to converting enzyme inhibition. In the post-myocardial infarction group, correlations betweenthe two methods were variable and much poorer than in the chronicheart failure group (r=0·54, P=0·01 and r=0·74,P=0·002 on consecutive days). Furthermore, captoprilmediatedincrements in effective renal plasma flow by the two techniqueswere unrelated (r= – 0·19, P=0·59). In thisgroup ¹²⁵I-orthoiodohippurate elimination significantly exceededpara-aminohippurate clearance (P<0·05). This reversedassociation and the weaker relationships between methods inpost-infarction as compared to chronic heart failure patientsmay be related to interference by thrombolytic or aspirin treatments.     

Effect of 48-h intravenous trimetazidine on short- and long-term outcomes of patients with acute myocardial infarction, with and without thrombolytic therapy. A double-blind, placebo-controlled, randomized trial

Aims To compare the effect of trimetazidine (TMZ) versus placeboadministered during the acute phase of myocardial infarctionon long- and short-term mortality. Methods and Results EMIP–FR (European Myocardial InfarctionProject–Free Radicals) was a prospective, double-blind,European multicentre trial in which 19725 patients, presentingsymptoms of acute myocardial infarction within the previous24h were randomized. Stratification was according to thrombolytictherapy (56%) or not (44%). An intravenous bolus injection oftrimetazidine (40mg) was given just before or simultaneouslywith thrombolysis, followed by continuous infusion (60mg.24h^–1)for 48h. Overall, no difference was found between trimetazidineand placebo for the main end-point, short-term (35-day) mortality,(P=0·98) in an intention-to-treat analysis. This wasthe result of opposing trends in the two strata. Thrombolysedpatients showed a tendency towards more short-term deaths withtrimetazidine, compared to placebo (trimetazidine: 11·3%,placebo: 10·5%, P=0·15) and non-thrombolysed patientsthe converse (trimetazidine: 14·0%, placebo: 15·1%,P=0·14). In a per-protocol analysis the beneficial effectof trimetazidine for non-thrombolysed patients became statisticallysignificant (trimetazidine: 13·3%, placebo: 15·1%,P=0·027). Conclusion Trimetazidine does not reduce mortality in patientsundergoing thrombolytic therapy; however, it might have somebeneficial effect for non-thrombolysed patients.     

Serum myoglobin for the early non-invasive detection of coronary reperfusion in patients with acute myocardial infarction

The ideal non-invasive method for detectmg coronary reperfusionhas not yet been established. In 63 patients with acute myocardialinfarction, serum myoglobin and creatine kinase-MB were measuredevery 15mm. Thrombolytic treatment was given (n=52) and acutecoronary angiography showed a patent infarct-related arteryin 49 patients while 14 patients had no coronary reperfusion.Median time to peak serum myoglobin was shorter (reperfusiongroup 178 mm vs no reperfusion group 480 min, P<0·0001)than time to peak serum creatine kinase-MB (reperfusion group550 mm vs no reperfusion group 1080 min, P<0·0001),P<0·0001. Myoglobin appearance rate, calculated asthe concentration at 2 h divided by baseline values (Mb₂/Mb₀)was highest in the reperfusion group (4·0 vs 1·6),P<0·001. An earlier proposed index, Mb₂/Mb₀>2·4 for identificationof reperfusion 2 h after thrombolytic therapy, showed predictivevalues of positive and negative tests of 0·94 and 0·44,respectively. Combining this mdex with signs of medium to largerinfarct size (Mb₂>200 µg . 1^–1)increased thepredictive value of the negative test to 1·00. In patientswith signs of minor mfarcts (Mb₂ <200 .µg .1^–1)the predictive values of positive and negative tests were 0·94and 0·79 respectively, 5 h after onset of thrombolytictherapy. An early rise and a peak in serum myoglobin values seems tobe a reliable and simple non-invasive indicator of successfuland unsuccessful reperfusion therapy. (Eur Heart J 1996; 17: 399–406)     

Impact of dietary sodium intake on left ventricular diastolic filling in early essential hypertension

Aims Dietary sodium intake modulates left ventricular hypertrophyin established essential hypertension independent of blood pressurelevel. We conducted this study to elucidate the relationshipbetween sodium intake and left ventricular structural or functionalchanges in early essential hypertension. Methods Forty-four young male patients (age 25·9±2·6years) with mild essential hypertension that had never beentreated and 45 normotensive male control subjects of similarage were examined. Dietary sodium intake was measured from 24hurinary sodium excretion, blood pressure from 24h ambulatorymonitoring (SpaceLabs 90207), left ventricular structure from2-D guided M-mode echocardiography, and diastolic filling ofthe left ventricle (as the main compound of diastolic functionin a young population) by pulse-wave Doppler sonography. Results In hypertensive patients, daily sodium excretion correlatedwith the ratio of late (A) to early (E) maximum velocity (VmaxA/E; r=+0·27,P=0·07), velocity time integrals(A/E; r=+0·54,P<0·001) as well as atrial contribution,as a percent of left ventricular filling (VH ATCO; r=+0·52,P<0·001)independent of heart rate, whereas the opposite correlationswere observed in normotensives (allP<0·001). Stepwisemultiple regression analysis confirmed these results. Sodiumexcretion emerged as the strongest independent determinant ofimpaired diastolic filling in hypertensive patients (velocitytime integrals A/E: R²=0·49, ß=+0·57,P=0·0001;VH ATCO: R²=0·48, ß=+0·56,P<0·0001;Vmax A/E: ns). In normotensive subjects, sodium excretion wasa similar strong, but inverse deter-minant of diastolic filling(velocity time integrals A/E: R²=0·40, ß=–0·43,P=0·0028).Heart rate was a strong determinant of diastolic filling inhypertensive patients (ß=+0·55,P=0·0002)and in normotensive subjects (ß=+0·34,P=0·011).Left ventricular mass and end-diastolic volume index were notrelated to diastolic filling in either group. Conclusion In early essential hypertension, sodium excretion is correlatedwith impaired left ventricular diastolic filling independentof left ventricular mass. The renin-angiotensin-aldosteronesystem might be a mediator of the observed correlation.     

Dyspnoea and exercise intolerance during cardiopulmonary exercise testing in patients with univentricular heart: The effects of chronic hypoxaemia and Fontan procedure

BACKGROUND: Patients with univentricular hearts have decreased exercisetolerance and may demonstrate exertional dyspnoea. It is notknown if chronic hypoxaemia exacerbates exercise intoleranceand contributes to symptomatic limitation. The extent to whichsurgical correction of a right-to-left shunt by a Fontan-typeprocedure can increase exercise tolerance by reducing arterialdeoxygenation is not well documented. The cardiopulmonary exerciseresponses and the symptomatic status in two groups of univentricularpatients, those who are cyanotic and those who are acyanoticwith Fontan-type circulation, were compared. METHODS AND FINDINGS: Cardiopulmonary exercise testing was performed in 10 univentricularpatients with rest or stress-induced cyanosis (age 30·5±2·3[SE] years; 5 men) who had palliative or no surgery and eightpatients (age 29·4±1·5 years; 4 men) withFontan-type circulation. Peak oxygen consumption was comparablein both groups of univentricular patients (21·7±2·5vs 21·0±1·9 ml. kg^–1 . min^–1,P=0·85) but was less than an age-matched group of 10healthy subjects (34·7±1·9 ml. kg^–1. min^–1, P<0·001 for both). Arterial oxygensaturation was 90·6% at rest in the cyanotic patientscompared with 95·1% in the Fontan patients (P<0·001)and at peak exercise, 66·2% compared with 90·5%(P<0·001). Using a modified Borg scale (0–10),the symptoms of dyspnoea and fatigue were also assessed duringexercise in the patient groups. The Borg scores for dyspnoeain the cyanotic and the corrected univentricular patients were,respectively, as follows: Stage 1: 0·5 vs 1·7;P=0·04; Stage 2: 1·8 vs 2·3, P=0·5;Stage 3: 3·0 vs 3·5, P=0·7; Peak Exercise:4·9 vs 4·8, P=0·9. In addition, the Borgscores for fatigue were: Stage 1: 0·4 vs 1·6,P=0·08; Stage 2: 2·0 vs 2·2, P=0·9;Stage 3: 3·0 vs 4·3, P=0·5; Peak Exercise:4·9 vs 5·4, P=0·5. The major limiting symptomat peak exercise was dyspnoea in four cyanotic patients comparedwith one in the Fontan group (Chi-square 0·982, P>0·10).The arterial oxygen desaturation at peak exercise in the cyanoticpatients limited by dyspnoea was not different from those limitedby fatigue (67·5±10·1% vs 66·7±13·7%,P=0·92). Exercise tolerance was also not related to thearterial oxygen saturation at peak exercise (r=0·47,P=0·17) in these patients. CONCLUSION: Despite correction with Fontan-type surgery, the exercise toleranceand symptoms of these univentricular patients remained similarto those who were cyanosed. Cyanotic patients have adjustedto chronic hypoxaemia and it does not appear to determine theexercise tolerance or the genesis of dyspnoea in these patients.Further randomized prospective studies are required to investigatethe long-term benefits of Fontan-type procedures in these patientson exercise tolerance, symptoms and prognosis.     

A randomized trial of a fixed high dose vs a weight-adjusted low dose of intravenous heparin during coronary angioplasty

AIMS: Prospectively to compare success rate and complications in percutaneoustransluminal coronary angioplasty using two doses of heparin. METHODS AND RESULTS: Four hundred patients undergoing coronary angioplasty were randomlyassigned to receive 15 000 IU (group A) or 100 IU. kg ^–1(group B) of heparin. The angioplasty success rate was 95% inboth groups. Stents were placed in 28·5% and 26·5%of patients in groups A and B, respectively (P=0·73).The primary endpoint (freedom from death, myocardial infarction,unplanned revascularization or bailout stenting) occurred in91% vs 95% of patients in groups A and B, respectively (oddsratio: 1·88, 95% CI: 0·80—4·50, P=0·12).Haemoglobin loss was 0·36 ± 1 and 0·27± 0·9 g. dl ^–1 in groups A and B, respectively(P=0·37). The time to sheath removal (735 ± 265vs 558 ± 246 min) and the time to transfer to a stepdownunit (12·7 ± 4·5 vs 9·8 ±4·2 h) were longer in groups A (P=0·0001 for bothcomparisons). CONCLUSION: A weight-adjusted low dose of intravenous heparin is at leastas safe as a fixed high dose for coronary angioplasty. It allowsearlier sheath removal and discharge to a stepdown unit.     

Components of the insulin resistance syndrome are associated with progression of atherosclerosis in non-grafted arteries 5 years after coronary artery bypass surgery

Aims Risk factors for progression of atherosclerosis in non-graftedcoronary arteries were examined in a prospective 5-year follow-upstudy of 228 consecutive coronary artery bypass surgery patients,with the main emphasis on insulin resistance syndrome. Methods and Results Serum lipids and lipoproteins were measured pre-operativelyand 1, 2, 3 and 5 years after surgery; and a baseline oral glucosetolerance test with plasma insulin determinations was performedpre-operatively. Progression of atherosclerosis was assessedby means of computer-based quantitative coronary angiography.Compared to subjects without progression, the patients withprogression of atherosclerotic lesions had a higher body massindex both at baseline (P=0·022) and at 5 years (P=0·007),were more often treated for hyper-tension at baseline (P=0·008)and at 5 years (P=0·012), used diuretics more often duringthe follow-up period (P=0·002), had a larger blood glucosearea under the curve (P=0·015) and a lower insulin sensitivityindex (P=0·006) in the baseline oral glucose tolerancetest, had a higher serum total cholesterol concentration atbaseline (P=0·044), and a higher serum triglyceride concentration(P=0·005) during the whole follow-up period. Clusteringof the components of insulin resistance syndrome at baselinewas more frequently found in patients with progression of atheroscleroticlesions than in patients without progression (P=0·025).For example, for patients with 1 component, the risk of progressionwas 17%, while for patients with 5 components the risk was 67%.As compared to the other patients, those with new atheroscleroticlesions had a lower insulin sensitivity index at baseline (P=0·033),and a lower serum high density lipoprotein cholesterol concentrationduring the follow-up period (P=0·033). Conclusion In addition to high serum cholesterol, the components of theinsulin resistance syndrome are associated with progressionof atherosclerosis in non-grafted coronary arteries 5 yearsafter coronary artery bypass surgery     

Risk stratification by pharmacological stress echocardiography in a primary care cardiology centre: Experience in 1082 patients

Aim In this study we sought to determine the safety, feasibilityand prognostic value of pharmacological stress echocardiographyperformed in a primary care cardiology centre, populated byunselected patients evaluated with the aid of limited financialand technological resources. Methods and Results The study population was 1082 patients undergoing pharmacologicalstress echocardiography with either dipyridamole (n=714) ordobutamine (n=368) for the evaluation of known or suspectedcoronary artery disease. The echocardiogram was positive in284 (26%) patients. Two sustained ventricular tachycardias,reversible by antidote, occurred during stress testing. Limitingischaemia-independent side effects occurred in 1·5% dipyridamoleand in 2·4% dobutamine stress echocardiograms. Duringfollow-up (33±18 months), 17 cardiac deaths and 27 non-fatalmyocardial infarctions occurred. One hundred and twenty-sevenpatients underwent coronary revascularization, of whom 105 (37%)had a positive and 22 (3%) a negative stress testing result(P<0·0001). At Cox analysis, allowing for 14 clinicaland stress-echo variables, the independent predictors of cardiacdeath were, in decreasing order, a positive stress testing result(Odds ratio [OR]=6·0), resting wall motion score index(OR=5·7), age greater than 65 years (OR=4·9),previous Q-wave myo-cardial infarction (OR=3·5), andhypercolesterolaemia (OR=2·7). The 4-year survival ratewas 99·2% for patients with a negative and 89·8%for patients with a positive stress testing result (P=0·1096).When cardiac hard events (cardiac death and non-fatal myocardialinfarction) were considered as end-points, the following variableswere independently associated with prognosis: positive resultof stress testing (OR=3·1), hypercolesterolaemia (OR=2·4),and resting wall motion score index (OR=2·7). The 4-yearinfarction-free survival rate was 97·0% for patientswith a negative and 81·4% for patients with a positivestress testing result (P=0·1096). Conclusions Pharmacological stress echocardiography with either dipyridamoleor dobutamine was safe and feasible, providing an excellenttool for prognostic assessment of coronary artery disease ina primary care cardiology centre.The European Society of Cardiology     

Superiority of mitral valve repair in surgery for degenerative mitral regurgitation

OBJECTIVES: We aimed to assess the influence of type of operation on outcomein degenerative mitral regurgitation. METHODS: We compared outcomes in 278 consecutive patients who underwentmitral valve repair (167 patients), replacement with subvalvularpreservation (22 patients) and without subvalvular preservation(89 patients) for degenerative mitral regurgitation. RESULTS: There was a trend towards lower mortality with repair and replacementwith subvalvular preservation compared to replacement withoutsubvalvular preservation. Thirty-day mortality was 1·2%vs 0·0% vs 4·7% (ns) respectively. Six-year survivalwas, respectively, 67·8±7·4% (P=0·088)vs 80·8±11·0% (P=0·25 vs 63·3±5·9%for all-cause death, 78·5±6·8% (P=0·063)vs 95·5±4·4% (P=0·092) vs 67·6±5·9%for all complication-related death and 80·5±6·9%(P=0·076) vs 100·0±0·0% (P=0·045)vs 72· ± 5·8% for complication-relateddeath due to myocardial failure. Multivariate analysis confirmedindependent beneficial effects from repair compared to replacementwithout subvalvular preservation on complication-related death(hazard ratio 0·42, P=0·010) and death from myocardialfailure (hazard ratio 0·40 P=0·014), and fromrepair compared to mechanical replacement on thromboembolism(hazard ratio 0·45, P=0·029) and anticoagulation-relatedhaemorrhage (hazard ratio 0·19, P=0·026). CONCLUSIONS: Mitral valve repair is superior to replacement. The greatestsurvival advantage is in reduced mortality from myocardial failure.Repair should be the operation of choice for degenerative mitralregurgitation.     

Conversion of atrial fibrillation to sinus rhythm and rate control by digoxin in comparison to placebo

AIMS: A randomized, double-blind study with a high dose of digoxinadministered intravenously for conversion of atrial fibrillation(not due to haemodynamic alterations) to sinus rhythm, and forrate control in converters and nonconverters was set up. Outcomemeasures were conversion within 12 h; time to conversion; earlyrate control; and stable slowing within 12 h. METHODS: We studied 40 patients with recent onset (<1 week) atrialfibrillation; controls received saline intravenously, the otherpatients digoxin 1·25 mg. RESULTS: One patient converted before digoxin administration. Conversionoccurred in 9/19 patients on digoxin and in 8/20 on placebo(ns). The mean time to conversion tended to be shorter onlyfor digoxin. Two late conversions on placebo were observed within24 h. Heart rate during atrial fibrillation decreased after30 min for converters and non-converters (P<0·05).For all patients on digoxin, heart rate after 30 min was lowercompared to baseline (P<0·002) and to placebo (P<0·02).Persistent, stable slowing occurred only in 3/10 non-converterson digoxin (P<0·05), and two patients developed bradyarrhythmias.QTc was shortened immediately after conversion in all patients.Converters had baseline characteristics similar to those ofnon-converters. CONCLUSIONS: Intravenous digoxin offers no substantial advantages over placeboin recent onset atrial fibrillation with respect to conversion,and provides weak rate control.     

Pre-hospital diagnosis of myocardial infarction: an opportunity to improve outcomes?

Ortolani et al.¹ report on the potential impact of pre-hospitaldiagnosis of ST-elevation myocardial infarction (STEMI). Theauthors compared the different routes of referral taken by patientswho were transferred for primary percutaneous coronary intervention(PCI). A total of 658 STEMI patients were studied and threepredefined referral routes were compared: pre-hospital diagnosisand direct transportation (for patients within 90 min driveof the PCI centre, n=166), diagnosis at the interventional hospitalemergency department (n=316), or diagnosis at local hospitalsbefore transportation (n=176). The main finding of the studywas that patients who had a pre-hospital paramedic and doctorwith telemedicine transmission of STEMI and direct transferfor primary PCI had a significant reduction in ‘treatmenttime’ (from onset of     

Prognostic value of left ventricular volume response during dobutamine stress echocardiography

AIMS: An abnormal left ventricular volume response during dobutamineechocardiography identified patients with severe coronary arterydisease. The aim of the study was to assess the prognostic valueof left ventricular volume changes during dobutamine stressechocardiography in 136 patients. MEHTODS AND RESULTS: Endpoints were defined as spontaneous cardiac events at follow-up.Left ventricular end-diastolic and end-systolic volume changes(abnormal response: >10% and >20> decrease, respectively)were compared with other clinical and stress test variables.During 18±7 months of follow-up, 31 cardiac events occurred:12 hard events (cardiac death [n=6 myocardial infarction [n=6])and 19 soft events (unstable angina [n=16] congestive heartfailure [n=3] End-diastolic volume response (P=0·006),diabetes (P=0·008), inducible wall motion abnormalities(P=0·024), end-systolic volume response (P=0·039)and inducible angina (P=0·038) were related to a greaterlikelihood of cardiac events. The Cox regression analysis revealedend-diastolic volume response (odds ratio: 3·0; CI 1·44–6·32)and diabetes (odds ratio: 2·7; CI 1·28–5·69)to be independent predictors of spontaneous cardiac events.Diabetes (odds ratio: 4·0; CI 1·26–12·80)and >40% baseline ejection fraction (odds ratio: 2·21;CI 1·14–4·29) were independent predictorsof hard events. CONCLUSIONS: An abnormal end-diastolic volume response during dobutaminestress echocardiography identifies patients with an unfavourableoutcome; they should be considered for more accurate prognosticstratification.     

Randomized placebo-controlled study of the effects of simvastatin on haemostatic variables, lipoproteins and free fatty acids

The Oxford Cholesterol Study is a randomized placebo-controlledtrial designed primarily to assess the effects of simvastatinon blood cholesterol levels and side-effects in preparationfor a large, long-term trial of the effects of cholesterol-loweringdrug therapy on mortality. At present there is only limitedevidence from randomized comparisons of the effects of HMG-CoAreductase inhibitors, such as simvastatin, on thrombogenic,as distinct from atherogenic, pathways in coronary heart disease.The present sub-study was carried out to assess the effectsof simvastatin on a range of haemostatic variables, as wellas on free fatty acids and on lipoprotein fractions not studiedin detail previously. At an average of about 2 years after starting study treatment,non-fasting blood samples were obtained from a sequential sampleof 162 participants who had been randomly allocated to receive40 mg (54 patients) or 20 mg (57 patients) daily simvastatinor matching placebo treatment (51 patients). Only patients whoreported taking their study treatment and who were not knownto be diabetic or to be taking some other lipid lowering treatmentwere to be included. The principal comparisons were to be ofthose allocated simvastatin (i.e. 20 and 40 mg doses combined)vs those allocated placebo. Among patients allocated simvastatin, marginally significantlower factor VII antigen levels (12·10%±6·08of standard; 2P<0·05) and non-significantly lowerfactor VII coagulant activity (8·24%±4·99of standard) and fibrinogen concentrations (0·10±0·08g.l^–1) were observed. In contrast, plasminogen activatorinhibitor activity was significantly higher (2·62±1·03IU; 2P<0·01) among patients allocated simvastatin.No significant differences were seen in the other haemostaticfactors studied (e.g. prothrombin fragment 1·2, factorXII and C$$$ inhibitor). Total free fatty acid concentrationwas marginally significantly reduced (2P=0·02) with simvastatin,but none of the reductions in individual free fatty acids wassignificant. Lipoprotein fractions were only measured amongpatients allocated 40 mg daily simvastatin or placebo. Comparedwith placebo, simvastatin produced significant decreases notonly in LDL cholesterol (1·74±0·15 mmol.1^–1;2P<0·0001) but also in VLDL cholesterol (0·28±0·08mmol.1^–1; 2P<0·001) and IDL cholesterol (0·17±0·03mmol.1^–1; 2P<0·0001). There were also lowertriglyceride levels associated with LDL (0·07±0·01mmol.1^–1; 2P<0·0001), IDL (0·03±0·01mmol.1^–1; 2P<0·01) and VLDL (0·27±0·14;2P=0·05). The effects of simvastatin on haemostatic variables appear tobe far less marked than its lipid effects. Given the associationsof haemostatic factors with coronary heart disease incidence,larger randomized comparisons of the HMG-CoA re1ductase inhibitors(and of the newer fibrates, which may produce greater effects)are needed to provide more reliable estimates of the extentto which they influence these variables.