[Coronary microvascular dysfunction and aortic stenosis: an update]. / Dysfonction microcirculatoire coronaire et rétrécissement aortique : mise au point.

The coronary microcirculatory impairment is a key feature of the pathophysiology of aortic stenosis (AS), the most operated valvular disease over the world. Several studies showed this coronary microcirculatory impairment in AS, using different tools and protocols, in various patient population of AS. This article will review the impairment of the coronary microcirculation in AS underlining its multifactorial origin, its functional part related to the hemodynamic consequences of AS, its complex relationship with left ventricular hypertrophy, and its potential diagnostic and prognostic value.

[Management of acute coronary syndromes in a new French coronary intensive care unit. The first four years of activity in the GRACE registry (Global Registry of Acute Coronary Events)]. / Evaluation des quatre premières années d'activité d'une unité de soins intensifs cardiologiques pour la prise en charge des syndromes coronaires aigus comparativement aux données régionales du registre GRACE (Global Registry of Acute Coronary Events).

UNLABELLED: The GRACE registry provides the opportunity to analyse management of acute coronary syndromes in the real word and the impact of hospital characteristics. In this setting, we compare the activity of a new coronary intensive care unit with regional data. METHODS: From January 2000 to December 2003, 376 eligible patients were involved (22% of regional inclusion). GRACE standard diagnosis were the following, for our centrer (for the cluster): ST elevation myocardial infarction 28% (37%), non-ST elevation myocardial infarction 32% (31%), unstable angina 33% (24%). Demographic characteristics were similar with a median age of 64 (vs 66) and a large majority of male (74 vs 81%). Medical history and cardiovascular risk factors were comparable. Predictors of hospital mortality were observed at the same rate: cardiogenic shock (3 vs 3%), congestive heart failure > Killip 2 (4 vs 4%), left ventricular ejection fraction (LVEF) lower than 40% (17 vs 16%), recurrent ischemic symptoms (8 vs 8%). Coronary artery bypass grafts were required in 5% (vs 2%). RESULTS: Drugs prescription rates were similar: aspirin at admission (95%) and at discharge (95%), betablocker at admission (70%) and at discharge (85%), statin at admission (< 30% in 2000, > 60% in 2003) and at discharge (< 60% in 2000 and > 80% in 2003), ticlopidin-clopidogrel at admission (< 20% in 2000 and > 40% in 2003), ACE inhibitor for LVEF < 40%, intravenous GPIIblIIa, and low molecular weight heparin (90%). Cardiac catheterisation (90%) and percutaneous coronary interventions (80%) were performed at the same rates in our center and in the cluster. Hospital death was similar (2 vs 4%). Discharge status was home for a large majority of patients (63 vs 76%). The median length of stay was five days and shorter than three days for patients with unstable angina. CONCLUSION: Based on GRACE registry data, the present evaluation revealed that our new center offered evidence-based medical and interventional therapy in patients with acute coronary syndromes at the same level than experienced institutions with similar results for hospital death and length of stay.

[Results of heart surgery with extracorporeal circulation in octogenarians]. / Résultats de la chirurgie cardiaque avec circulation extracorporelle chez l'octogénaire.

Cardiac surgery in the octogenarians is increasing in the industrialized countries and therefore represents a growing population. In order to better define the benefits of cardiac surgery in this population, we reviewed all consecutive octogenarians patients operated during the last 10 years. Out of 3,409 patients operated between January 1990 and December 1999, we identified 215 patients (6.3%) aged 80 years or more. Median age was 82.4 +/- 2.45 years, and 52.6% were males. Preoperatively, 52% were in New York Heart Association functional class II, 19.3% in class III, and 28.3% in class IV, with a mean Euroscore score of 7.5 +/- 2.6. Among them, 113 patients (52.5%) had isolated aortic valve replacement, 66 patients (30.6%) had isolated coronary artery bypass graft, 22 patients (10.2%) had aortic valve replacement combined with CABG, and 14 patients (6.5%) had mitral valve operation. The overall hospital mortality was 8%, and multivariate analysis revealed as risk factor for mortality aortic valve replacement combined with coronary artery bypass graft. Median follow up was 36.7 months, with 86% survival at 1 year, 59% at 5 years, and 40% at 7 years. Survival was reduced when aortic valve was combined with revascularisation. Quality of life was improved in 72% of patients. We conclude that for selected octogenarians cardiac surgery can be performed with an acceptable mortality and improves both survival and quality of life.

Antistreptokinase platelet-activating antibodies are common and heterogeneous.

BACKGROUND: Platelet activation by antistreptokinase (SK) antibodies could impair the clinical effect of SK administration. OBJECTIVE: To better describe anti-SK antibodies with particular emphasis on procoagulant activities as a result of platelet activation. PATIENTS AND METHODS: Sera were collected from 146 patients with coronary artery disease: non-SK-treated, 95 from mainland France, 31 from French Polynesia; 20 patients from mainland in year 2 after SK treatment. Serum-induced SK-dependent platelet activation resulting in procoagulant activities was assessed with washed platelets from five donors representative of the known patterns of reactivities to IgG. RESULTS: Concentrations (2-5252 microg mL(-1)) and fibrinolytic neutralization titres (< 10 to > 1280) were found in the expected wide range and correlated (rho = 0.66, P < 0.0001). Platelet activation was detected with 145 samples, but varied in intensity and pattern (depending on the donors), although there was no systematic hierarchy; it was presumably due to IgG (inhibited by an IgG Fc receptor-blocking antibody and recovered in the IgG fraction) and only partially affected by aspirin. Marked platelet activation could be detected in samples with concentration as low as 2 microg mL(-1), and/or no detectable neutralizing titers. The way of immunization to SK was not found to influence the functional profile of antibodies. CONCLUSION: Anti-SK platelet-activating antibodies are widespread, heterogeneous, poorly predictable on the basis of their antifibrinolytic effect and strong enough to trigger procoagulant activities. Their clinical relevance should be formally assessed, using patients' own platelets for detection owing to the variation of platelet reactivity.

[Iatrogenic lesions of the left main coronary artery]. / Lésions iatrogéniques du tronc commun coronaire gauche.

Reoccurrence of ischemic events several months after a percutaneous transcutaneous coronary angioplasty is usually due to a restenosis. Coronary angiography rarely shows a new stenosis on another site or on the left main coronary artery. In this series, we report 5 cases of left main coronary artery stenosis which have occurred from 3 to 12 months after a prior percutaneous angioplasty. This phenomenon which has previously been described after direct cannulation of the coronaries ostia during aortic valve replacement in the 70'. This complication is related to intimal damage caused by traumatic manipulation of the left main, which can be either already minimally altered or normal. This complication is rare after percutaneous transcutaneous coronary angioplasty (0.2-1.7%) according to various series. We compare our cases to the published cases in the literature.

[Perforation of the aorta after percutaneous closure of an atrial septal defect with an Amplatz prosthesis, presenting with acute severe hemolysis]. / Perforation de l'aorte après fermeture percutanée d'une communication interauriculaire par prothèse d'Amplatz, révélée par une hémolyse aiguë sévère.

We report a case of aortic perforation three weeks after transcatheter occlusion of an atrial septal defect (ASD) by an Amplatzer device. Revealed by acute hemolysis, this complication needed an emergency surgical operation. The fistula between the no coronary Valsalva sinus of the aorta and the left atrium was repaired. The ASD was closed by patch. This serious accident should consider a short antero-superior rim as a risk factor for aortic perforation in transcatheter closure for ASD.

[Iatrogenic dissection of the left main artery treated by direct stenting]. / Dissection iatrogène du tronc commun traitée par direct stenting.

A 70-year-old woman was referred to the department due to a symptomatic severe calcific-aortic stenosis. During pre-operative trans-radial approach coronagraphy occurred a iatrogenic dissection of the left main artery with total occlusion and cardiac arrest (asystole). Successful resuscitation is achieved with an emergency strategy of percutaneous direct stenting revascularization combined with cardiopulmonary resuscitation manoeuvres.

Ten-years' clinical experience with the Sorin Pericarbon valve.

BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate 10 years' results obtained with the Pericarbon pericardial bioprosthesis. METHODS: Between September 1988 and December 1997, 277 patients (mean age 75.8 +/- 8.5 years) received a total of 287 Pericarbon pericardial valves. Of these patients, 224 (80.8%) underwent single aortic valve replacement (AVR) and 39 single mitral valve replacement (MVR); one patient had a tricuspid valve replacement (TVR), three patients had a pulmonary valve replacement (PVR) and 10 had both aortic and mitral valve replacement (DVR). Associated cardiac procedures were performed in 86 patients (31.0%), mainly coronary artery bypass graft (n = 71). Mean patient follow up was 4.9 +/- 2.6 years; total cumulative follow up was 1,221.4 patient-years. RESULTS: The overall hospital mortality rate was 10.1%. There were 50 late deaths (20.1%), four (1.6%) being valve-related. The patient survival rate at 10.8 years was 60.0 +/- 4.5% for AVR and 46.5 +/- 11.9% for MVR. Freedom from valve-related death at 10.8 years was 97.6 +/- 1.1% for AVR and 100% for MVR. Freedom from structural valve deterioration was 96.1 +/- 2.7% for AVR and 100% for MVR. Freedom from embolic events was 96.0 +/- 1.5% for AVR and 100% for MVR. In total, 16 patients needed reoperation, three for stenosis due to dystrophic calcification, six for endocarditis and seven for paravalvular leak. Freedom from reoperation was 89.9 +/- 4.2% for AVR and 80.6 +/- 7.3% for MVR. CONCLUSION: These results show that, over a period of up to 10 years, the Pericarbon pericardial bioprosthesis constitutes an excellent and safe replacement valve.

Relationship between resting 201Tl reverse redistribution, microvascular perfusion, and functional recovery in acute myocardial infarction.

UNLABELLED: 201TI reverse redistribution is a common finding early after reperfusion therapy for myocardial infarction. Its mechanism and clinical implications remain unclear. The aim of this study was to clarify the relationships between reverse redistribution, microvascular perfusion, and myocardial viability. METHODS: Resting, 10-min-postinjection, and redistribution 201TI data obtained for 33 patients 8 and 42 d after the onset of acute myocardial infarction were compared with echocardiographic wall motion measured acutely and on day 42. Microvascular perfusion was assessed by myocardial contrast echocardiography performed 10 min after restoration of complete patency of the infarct artery. RESULTS: Marked significant reverse redistribution was found on day 8 (absolute change, 7.5%+/-7.9% of the 10-min-postinjection defect size; P<5x0.000001) and significantly decreased on day 42 (2.7%+/-6.8%; P = 0.004 between days 8 and 42). The 10-min-postinjection defect size best predicted the final infarct size on day 42 and was closely related to microvascular perfusion. Patients with adequate reperfusion had a smaller postinjection defect on day 8 (21.1%+/-14.6%) and a larger reverse redistribution (10.2%+/-6.1%) than did patients with no reflow (35.3%+/-13% and 3.2%+/-9.2%, respectively; P<0.04 for both). CONCLUSION: Reverse redistribution was marked early after myocardial infarction in patients with complete patency of the infarct artery and decreased in subsequent weeks. Reverse redistribution was associated with restoration of adequate microvascular reperfusion and with myocardial salvage and viability. The early postinjection scans on day 8 were the relevant images for assessing myocardial salvage and predicting wall motion recovery.

[Coronary subclavian steal syndrome after internal mammary artery bypass grafting. A cause of severe postoperative recurrent myocardial ischemia]. / Syndrome de vol coronaire sous-clavier après pontage mammaire interne gauche sur l'artère interventriculaire antérieure. Une cause d'ischémie myocardique résiduelle sévère postopératoire.

A 65-year-old underwent a triple bypass: internal artery mammary-descending coronary artery, aorta diagonal-lateral coronary (sequential). Three weeks later he started to have severe angina pectoris with ST depression in anterior EKG leads. A left transradial coronary angiography was performed. The examination showed a total occlusion of the left subclavian artery 2 cm after the aortic arch and a retrograde flow in the internal mammary artery (IMA). Via transfemoral approach, angiography showed the patency of the aorto-veinous sequential graft and a retrograde flow through anastomosis in the left mammary artery. The patient underwent a reimplantation of the IMA on the brachiocephalic artery. One month later the patient is doing well without chest pain. A coronary subclavian steal syndrome should be suspected in case of recurrent ischaemia after IMA bypass, particularly if there is more than 20 mmHg systolic pressure differential between the arms. Left transradial approach achieved diagnostic in case of total left subclavian artery occlusion.

Decreased no-reflow in patients with anterior myocardial infarction and pre-infarction angina.

AIMS: Pre-infarction angina is associated with better outcome after myocardial infarction. The aim of this study was to assess whether pre-infarction angina is associated with decreased no-reflow after coronary recanalization. METHODS AND RESULTS: Twenty-three patients underwent intracoronary myocardial contrast echocardiography during the acute phase of anterior myocardial infarction after successful recanalization, and before hospital discharge. Myocardial perfusion was graded semi-quantitatively in the area at risk (dyssynergic segments). Global left ventricular function was assessed by radionuclide angiography on days 8 and 42 and regional wall motion was assessed by 2D echocardiography on days 0 and 42. Fourteen patients had pre-infarction angina (angina less than 7 days before myocardial infarction) and nine did not. Baseline characteristics were similar in the two groups. The myocardial contrast echocardiography perfusion score in the area at risk after recanalization was higher in the patients with pre-infarction angina than in those without (0.72 +/- 0.19 vs 0.53 +/- 0.22, P=0.04), and the incidence of no-reflow (myocardial contrast echocardiography perfusion score < or =0.5) was lower (14% vs 56%, P=0.04). This difference persisted 8 +/- 2 days after myocardial infarction (0. 87 +/- 0.11 vs 0.69 +/- 0.26, P=0.04), and was associated with greater mid-term (day 42) improvement in left ventricular function in patients with pre-infarction angina than in those without, as assessed by changes in radionuclide left ventricular ejection fraction (+5.8 +/- 8.1% vs -3.3 +/- 4.6%, respectively;P=0.01) and by changes in regional wall motion score on 2D echocardiography (-0. 61 +/- 0.39 vs -0.24 +/- 0.17, respectively;P=0.04). CONCLUSION: Pre-infarction angina is associated with preservation of the microvasculature, reflected by reduced no-reflow. This may be a mechanism underlying greater recovery of left ventricular function in patients with pre-infarction angina.

[Harvesting of an internal saphenous graft for aorto-coronary bypass using video-surgery]. / Prélèvement du greffon saphène interne pour pontage aorto-coronaire par méthode vidéo-chirurgie.

Classical excision of saphenous vein grafts requires a continuous incision on the leg or the thigh or both. To minimise the trauma due to this method, an endoscopic method has been recently developed. The aim of this paper was to assess the benefits of this new method compared with the classical technique. One hundred and twenty patients requiring aorto-coronary grafts were included in this prospective study and divided into two groups according to the method of saphenous vein harvesting. Group A comprised 60 patients who underwent the classical method os saphenous vein harvesting and Group B 60 patients who benefited from the endoscopic method. No difference was observed between the two groups with respect to mean age, sex ratio, history of diabetes and obliterative arterial disease of the lower limbs. Parsonnet index number of bypass grafts and length of vein excised. The length of the skin wound in group A was 30.8 +/- 8.5 cm compared with only 4.1 +/- 1 cm in Group B (p = 0.006) but the harvesting time was longer by endoscopy (55.7 +/- 23.7 minutes: 72.5 +/- 22.6 minutes for the first 10 patients, 48.5 +/- 24.7 minutes for the last 50 patients) compared with the classical technique (39.8 +/- 6.6 minutes: p = 0.001). Moreover, patients who underwent videosurgery had less operative pain (8% versus 15%) (p = 0.001). The number of infectious complications was slightly lower in Group B (3.3%, 2/60, versus 10%, 6/60), (NS). The authors conclude that harvesting of the saphenous vein by videosurgery reduces postoperative pain and gives a more aesthetic result but with a slightly longer operative time at the beginning of the experience.

[Applications of contrast echocardiography in the acute phase of myocardial infarction]. / Applications de l'échocardiographie de contraste à la phase aiguë de l'infarctus du myocarde.

The present interest in myocardial contrast echocardiography is related to the development of new contrast agents which can be used intravenously and the perfection of new echocardiographic technologies. Amongst the potential applications of this technique, the study of myocardial perfusion in the acute phase of myocardial infarction is one of the most promising as shown by the experience acquired over several years with intracoronary contrast echocardiography. It allows assessment of the extent of the zones at risk before recanalisation, the presence of collateral vessels and, above all, the quality of myocardial reperfusion. The demonstration of the absence of effective reperfusion of the myocardial microcirculation, or the phenomenon of no-reflow, is one of the main advantages of contrast echocardiography and has been identified as an important independent prognostic factor. This technique could therefore become essential in the evaluation of methods for reducing the extent of microvascular damage. Although many questions remain unanswered about the ideal methods of performing and analysing intravenous contrast echocardiography, the preliminary results confirm the potential of the technique in non-invasive evaluation of myocardial reperfusion in the acute phase of myocardial infarction.

Acute assessment of microvascular perfusion patterns by myocardial contrast echocardiography during myocardial infarction: relation to timing and extent of functional recovery.

OBJECTIVE: To examine the relation between the initial microvascular perfusion pattern, as assessed by intracoronary myocardial contrast echocardiography (MCE), immediately after restoration of TIMI (thrombolysis in myocardial infarction) (TIMI) grade 3 flow during acute myocardial infarction, and the extent and timing of functional recovery in the area at risk. SETTING: Referral centre for interventional cardiology. METHODS: Intracoronary MCE was performed 15 minutes after TIMI grade 3 recanalisation of the infarct artery in 25 patients. Segmental myocardial contrast patterns were graded semiquantitatively (0, none; 0.5, heterogeneous; 1, homogeneous). Functional recovery was assessed by echocardiography on days 9 and 42. RESULTS: Among 174 myocardial segments in the area at risk, wall motion recovery on day 9 was observed in 40% of MCE grade 1 segments but there was no significant recovery in grade 0 or 0.5 segments. On day 42, recovery had occurred in 56% of MCE grade 1 segments (p < 0. 0001 v MCE grade 0 and 0.5; p = 0.0001 v MCE grade 1 on day 9), and 22% of MCE grade 0.5 segments (p = 0.02 v MCE grade 0; p = 0.0005 v MCE grade 0.5 on day 9); MCE grade 0 segments did not recover. Negative predictive value in predicting recovery by contrast enhancement was 95% and 89% by days 9 and 42, respectively. CONCLUSIONS: Contractile recovery occurs earliest in well reperfused segments. Up to one quarter of segments with heterogeneous contrast enhancement show wall motion recovery within the first six weeks. Myocardial perfusion after recanalisation in acute myocardial infarction, even if heterogeneous, is a prerequisite for postischaemic functional recovery. Thus preservation of acute myocardial perfusion is associated with more complete and early functional recovery.

Early changes in myocardial perfusion patterns after myocardial infarction: relation with contractile reserve and functional recovery.

OBJECTIVES: The purpose of this study was to assess early temporal changes in myocardial perfusion pattern by myocardial contrast echocardiography (MCE) and their relation to myocardial viability in patients with reperfused acute myocardial infarction (AMI). BACKGROUND: Myocardial contrast echocardiography no-reflow is associated with poor contractile recovery after AMI. However, little is known regarding early reversibility of microvascular dysfunction and its relation to myocardial viability. METHODS: Intracoronary MCE was performed immediately after reflow and 9 days later in 28 patients with a first AMI and successful coronary recanalization (Thrombolysis in Myocardial Infarction trial grade 3 flow). Semiquantitative contrast score and wall motion score (WMS) were assessed in each initially asynergic segment at initial and repeat MCE study. Low dose dobutamine echocardiography (DE) was performed at day 10, and follow-up (FU) rest echocardiography was performed 6 weeks later. RESULTS: Among 200 initially asynergic segments, 49% exhibited no or heterogeneous contrast enhancement at initial MCE versus 24% at restudy (p < 0.001). Three groups of segments were defined according to early changes in contrast pattern: group A, "sustained no-reflow" (n = 17); group B, improved contrast score (n = 68), and group C, "sustained reflow" (n = 112). Group A segments showed no improvement in WMS at FU. In contrast, group B segments showed significant improvement in WMS at FU (p < 0.0001), and exhibited more frequently contractile reserve at DE (36% vs. 6%, p = 0.02) and contractile recovery at FU (34% vs. 7%, p = 0.03) than group A segments. Group C segments exhibited contractile reserve and contractile recovery in 47% and 51% of segments respectively. CONCLUSIONS: Improvement in MCE perfusion pattern may occur after initial no-reflow in the days following reperfused AMI and is associated with preservation of contractile reserve and gradual regional functional recovery.

Left ventricular-arterial system coupling at peak exercise in dilated nonischemic cardiomyopathy.

We assessed the ventricular-arterial coupling at peak exercise in 20 patients with dilated cardiomyopathy (ejection fraction, 27+/-12%) and 7 normal subjects by radionuclide ventriculography during exercise, coupled with respiratory gas analysis. The end-systolic pressure-volume ratio, taken as an index of contractility, and the effective arterial elastance were calculated at rest and at peak exercise. The end-systolic pressure/volume ratio increased from 3.7+/-2.7 to 6.9+/-4.0 mm Hg/mL at peak exercise in the normal subjects, but did not change significantly (from 0.9+/-0.5 to 1.0+/-0.6 mm Hg/mL) in the patients. Arterial elastance did not change significantly in the patients (+17+/-32%, not significant [NS] vs rest) or in the normal subjects (+22+/-28%, NS vs rest). The change in ejection fraction during exercise correlated both with the end-systolic pressure/volume ratio and with effective arterial elastance changes (r=0.60 and 0.68, respectively). We conclude that ventricular arterial coupling is further altered at peak exercise in these patients because of the lack of increase in contractility and not of altered effective arterial elastance response.

Comparison of left ventricular responses to the six-minute walk test, stair climbing, and maximal upright bicycle exercise in patients with congestive heart failure due to idiopathic dilated cardiomyopathy.

Submaximal exercise tests have been advocated to assess exercise capacity in chronic heart failure, but hemodynamic responses have not been characterized. To determine left ventricular (LV) responses during submaximal exercise, the LV ejection fraction (EF) and volumes were evaluated by using an ambulatory radionuclide detector in 13 patients with idiopathic dilated cardiomyopathy during upright maximal graded bicycle exercise, stair climbing and a 6-minute walk test. The 3 tests elicited different responses in volumes and, to a lesser degree, in LVEF. The maximal bicycle exercise led to a decrease in LVEF from 22 +/- 9% to 17 +/- 8% (p <0.05), with marked increases in both end-diastolic volume (EDV) (+15 +/- 10%, p <0.001) and end-systolic volume (ESV) (+23 +/- 18%, p <0.001). Stair climbing tended to reduce LVEF (from 24 +/- 11% to 21 +/- 10%, p = 0.05), with a lesser increase in volumes, which was more marked for ESV (+8 +/- 9%, p <0.01) than for EDV (+4 +/- 4%, p <0.01). The 6-minute walk test did not significantly change LVEF (23 +/- 10% vs 22 +/- 10%), but increased both EDV (+10 +/- 6%, p <0.001) and ESV (+8 +/- 8%, p <0.01) moderately and proportionally. Exercise capacity indexes (peak oxygen consumption, maximal bicycle work rate, stair climbing time, and the distance covered during the 6-minute walk test) correlated significantly with one another. There was no correlation between submaximal exercise tolerance indexes and resting or exercise LVEF. This study shows that (1) LVEF changes are inadequate to report on LV volume changes during exercise; (2) the 3 tests induce different LV volume changes; (3) the 6-minute walk test induces significant changes in LV volumes but no change in LVEF.

[Myocardial viability: results of myocardial revascularization during the acute phase of myocardial infarction]. / Viabilité myocardique: résultats de la revascularisation myocardique à la phase aiguë de l'infarctus.

Complete coronary reperfusion after thrombolysis or primary angioplasty is associated with limitation of infarct size and conservation of left ventricular function. The area of viable myocardium recovers its function secondarily, the amount of recovery being related to the precocity of reperfusion. Patients with a patent artery in the acute stage do not all recover segmental contraction to the same extent. There are considerable discrepancies between coronary patency and myocardial perfusion. Myocardial perfusion, measured in the acute phase by myocardial contrast echocardiography is the best predictor of preservation of function. This suggests that microvascular lesions are a sign of the extent and irreversibility of myocardial damage. Modern treatment of infarction should not only restore coronary patency but also ensure effective myocardial reperfusion. The factors which determine recovery of ventricular function after reperfusion during the acute phase, are, in addition to early and complete coronary recanalisation and effective myocardial reperfusion: short duration of ischaemia, small size of the area at risk, collateral circulation, ability of the myocardium to withstand ischaemia, limitation of reperfusion injury. Other factors (smoking, pre-infarction angina, the occluded artery or method of reperfusion) may play a role but the role of confounding factors is always difficult to exclude.