Summary
Background
Myocardial infarction is rarely caused by non-occlusive thrombus in angiographically normal coronary arteries. The cases reported in the literature are scarce and follow-up was usually short. The efficacy and tolerability of the exclusively medical treatment strategy used in most cases remain unknown.
Aims
To evaluate efficacy of medical treatment and long-term prognosis in these patients.
Methods
We retrospectively selected and analysed patients hospitalized in our centre between 1998 and 2008 for myocardial infarction caused by non-occlusive thrombus in angiographically normal coronary arteries (defined as stenosis < 30%), who were exclusively medically treated. A long-term follow-up was performed. A review of the literature regarding such cases was carried out.
Results
Sixteen patients were identified; apart from smoking, they had few conventional cardiovascular risk factors. Two patients died in hospital. The 14 survivors were followed up for an average of 4.9 years and only one death (non-cardiac cause) and one stroke (related to supraventricular arrhythmia) occurred in this period. Medical treatment included the use of glycoprotein IIb/IIIa inhibitors in 75% of cases. The literature review revealed 36 similar cases due to multiple aetiologies–particularly coronary artery spasm and prothrombotic coagulopathies.
Conclusion
Patients with myocardial infarction secondary to non-occlusive thrombus in angiographically normal coronary arteries seem to have a good long-term prognosis after the acute phase when treated with an exclusively medical strategy. However, initial clinical presentation was often severe, leading to early in-hospital death.
Résumé
Contexte
Les infarctus du myocarde peuvent, rarement, être causés par des thrombus non occlusifs sur des coronaires angiographiquement normales. Les cas rapportés dans la littérature ont été rares et leur suivi souvent court. L’efficacité et la tolérance du traitement médical exclusif, utilisé dans la plupart des cas, restent inconnues.
Objectif
Évaluer l’efficacité du traitement médical et le pronostic à long terme chez ces patients.
Méthode
Nous avons rétrospectivement sélectionné et analysé les patients hospitalisés dans notre centre, entre 1998 et 2008, pour un infarctus du myocarde causé par un thrombus non occlusif sur coronaires angiographiquement normales définies par des sténoses inférieures ou égales à 30 % et traités exclusivement médicalement. Un suivi à long terme a été effectué. Une revue de la littérature sur les cas similaires a été réalisée.
Résultats
Seize patients ont été identifiés et hormis le tabagisme, ils avaient peu de facteurs de risques cardiovasculaires conventionnels. Deux patients sont décédés à l’hôpital. Les 14 survivants ont été suivis pendant 4,9 ans en moyenne, un décès de cause non cardiaque et un accident vasculaire cérébral relatif à un trouble du rythme supraventriculaire ont eu lieu. Le traitement médical comprenait l’utilisation des inhibiteurs des GPIIb/IIIa dans 75 % des cas. La revue de la littérature a révélé 36 cas similaires aux étiologies multiples, en particulier le spasme coronaire et les coagulopathies prothrombotiques.
Conclusion
Les patients avec infarctus du myocarde secondaire à un thrombus non occlusif sur coronaires angiographiquement normales semblent avoir un excellent pronostic à long terme après la phase aiguë lorsqu’ils ont été traités exclusivement médicalement mais la présentation clinique initiale fut souvent sévère conduisant à des décès hospitaliers précoces.
Background
Acute coronary syndromes include several clinical and anatomical aspects of coronary disease, especially including intracoronary thrombus. Percutaneous revascularization of thrombus-containing lesions is associated with increased incidence of death and myocardial infarction . However, intracoronary non-occlusive thrombi were rarely observed in patients without angiographic coronary lesions and have previously been proposed as a possible cause of myocardial infarction in those with normal coronary arteries . The development of interventional cardiology allowed these thrombi to be identified in the acute phase of coronary syndromes. In the literature, case reports were scarce and follow-up was usually for less than 6 months. Exclusively medical treatment was used in most cases but its efficiency and tolerability remain unknown. Our study investigated the characteristics, aetiologies and long-term follow-up of patients with intracoronary non-occlusive thrombus without angiographic coronary lesions, who were medically treated in the acute phase. A review of the literature reporting such cases was performed.
Methods
Our study
Patients who were admitted to our institution with myocardial infarction with or without ST-segment elevation were screened retrospectively from January 1998 to October 2008. Coronary angiograms were reviewed by two independent experienced angiographers. Sixteen patients were identified who had intracoronary thrombus without significant coronary stenosis (angiographically defined as more than 30%) and received exclusively medical treatment during the acute phase. The angiographic presence of a thrombus was defined as a non-calcified filling defect outlined on at least three sides by contrast media. We included patients with thrombus greater or equal to grade 2 , thrombolysis in myocardial infarction (TIMI) flow 2 or 3 and without significant coronary lesions (underlying or throughout the coronary tree; Fig. 1 ). Patients were excluded for the following reasons: if doubt remained about the underlying coronary lesion due to the thrombus being affixed to the artery wall; if they had an anatomical abnormality of the coronary arteries (dissection, ectasia); if they had thrombosis during the procedure; or if they required balloon angioplasty or stenting in the acute phase.
Age, sex, cardiovascular risk factors and left ventricular ejection fraction were recorded. Clinical conditions known to be associated with hypercoagulation, such as pregnancy, oral contraceptive or drug use, were searched for systematically. Coronary angiograms and treatments were detailed.
Follow-up was performed by telephone questioning of the patient’s general practitioner and cardiologist in February 2009. In case of lack of information this could be completed by interviewing the patients. The following data were analysed: death (cardiac death or all-cause mortality), recurrence of myocardial infarction, need for revascularization, heart failure, ventricular arrhythmia, bleeding complication, stroke, thromboembolic event, left ventricular ejection fraction and medical treatment.
Review of the literature
We conducted a manual review of case reports using the PubMed database. Unrestricted database searches until January 2009 were performed using the Medical Subject Headings (MeSH) term “coronary thrombosis”. Article references were reviewed in order not to miss other case reports. Some articles had several case reports, of which only one was selected.
We included case reports on patients with ST-segment or non-ST-segment elevation myocardial infarction, with angiographically confirmed thrombus greater or equal to grade 2, without proximal occlusion on the thrombus and with angiographically normal coronary arteries. Studies with insufficient information and those involving patients with angiographically atheromatous coronary lesions greater than 30%, anatomical abnormalities of the coronary arteries (dissection, ectasia), thrombosis during the procedure or post-mortem-visualized thrombus were excluded.
The following information was extracted from each study: first author; year of publication; journal; patient characteristics (sex, age, cardiovascular risk factors, Killip class); electrocardiogram; coagulation analyses; left ventricular ejection fraction; thrombus TIMI grade; localization; presence of distal embolizations; treatment; possible coronary angiography control; aetiology; and follow-up.
After a review of 1261 published articles, 196 were read in detail and 36 articles were finally selected ( Fig. 2 ). Similar cases were published by Burzotta et al. but were not included in this review because the patients were treated in our institution and were therefore included in our cohort.
Statistical analysis
All continuous variables are expressed as mean values ± standard deviations. Categorical variables are expressed as numbers of patients or percentages.
Results
Our cohort included 11 men and five women, with a mean age of 48 ± 14 years. Mean body mass index was 26.4 ± 4.8 (half had a body mass index > 25). Mean left ventricular ejection fraction was 56.8 ± 14.2% (range 20–76%). None of the patients had previous angina and more than 50% presented with ST-segment elevation on electrocardiogram at admission. Patient demographics and clinical characteristics at admission are summarized in Table 1 . The TIMI risk score was less or equal to 3 for all patients and the mean Global Registry of Acute Coronary Events (GRACE) score was 90 ± 27.
| Characteristic | |
|---|---|
| Baseline characteristics at admission ( n = 16) | |
| Men | 11 (69) |
| Previous angina pectoris | 0 |
| Systemic hypertension | 5 (31) |
| Diabetes mellitus | 0 |
| Hyperlipidaemia | 2 (12.5) |
| Current smoker | 9 (56) |
| Family history of coronary disease | 3 (19) |
| Systolic blood pressure (mmHg) | 121 ± 18 |
| Diastolic blood pressure (mmHg) | 76 ± 11 |
| Pulse (beats per minute) | 72 ± 12 |
| Heart failure | 4 (25) |
| Electrocardiogram | |
| ST-segment elevation | 9 (56) |
| Non-ST-segment elevation | 7 (44) |
| Cardiogenic shock | 3 (19) |
| Pharmacological treatments in acute phase | |
| Thrombolytic agents (patients with ST-segment elevation) | 2/9 (22) |
| Unfractionated heparin | 13 (81) |
| Low-molecular-weight heparins | 3 (19) |
| Aspirin | 15 (94) |
| Aspirin + clopidogrel or ticlopidine | 11 (69) |
| Glycoprotein IIb/IIIa inhibitors | 12 (75) |
| In-hospital deaths | 2 (12.5) |
| Pharmacological treatments at discharge ( n = 14) | |
| Aspirin | 14 (100) |
| Beta-blockers | 14 (100) |
| Angiotensin-converting enzyme inhibitors | 11 (79) |
| Statins | 13 (93) |
| Low-molecular-weight heparins | 10 (71) |
| Aspirin + clopidogrel or ticlopidine | 12 (86) |
All patients received curative anticoagulation in the acute phase and 75% received glycoprotein IIb/IIIa inhibitors for at least 12 hours. Seventy-one percent of the survivors received low-molecular-weight heparins for at least 7 days. All patients received aspirin and 86% had both aspirin and clopidogrel or ticlopidine at discharge ( Table 1 ).
Blood analysis showed severe renal insufficiency in one patient and slight renal insufficiency in four patients. Coagulation disorders were investigated in only three patients; the results were negative. One patient was treated for essential thrombocythaemia. Homocysteinaemia was analysed in half of our cohort; results were normal. Mean fibrinogen was 3.6 ± 1.5 g/L (range 2.1–6.8 g/L).
Retrospective analysis of coronary angiograms showed mostly high-grade thrombi ( Table 2 ). Coronary angiogram control was done in nine patients. Of the four controls done on day one, three showed persistent thrombi. The thrombi had disappeared on all controls done after the third day of hospitalization.
| Coronary angiogram characteristics | Number of patients (%) |
|---|---|
| Thrombus grade | |
| Grade 1 | 0 |
| Grade 2 | 1 (6) |
| Grade 3 | 7 (44) |
| Grade 4 | 8 (50) |
| Location | |
| Left anterior descending coronary artery | 7 (44) |
| Circumflex coronary artery | 1 (6) |
| Right coronary artery | 7 (44) |
| Left main coronary artery | 1 (6) |
| TIMI grade flow | |
| TIMI 2 | 3 (19) |
| TIMI 3 | 13 (81) |
| Distal embolization | 3 (19) |
| Multiple thrombi | 1 (6) |
Aetiologies were suspected in eight patients ( Fig. 3 ). Among patients with a found aetiology, one patient aged 31 years had presented with a stroke 6 years earlier but died within the first 24 hours and it was not possible to obtain a complete coagulation analysis. No patient was human immunodeficiency virus positive. Among patients without a found aetiology, five had cardiovascular risk factors other than smoking and five were smokers versus three and four, respectively, among patients with a found aetiology.
Two patients died in hospital: the first after 24 hours due to refractory shock after left ventricular assistance for irreducible ventricular fibrillation and the second after 2 months due to septic shock. Mean follow-up was 4.9 years (range 6 months to 10 years) for the remaining 14 patients. One patient died 6 years later from a non-cardiac cause (septic shock in myeloproliferative syndrome secondary to thrombocytosis). One patient presented with a stroke in atrial fibrillation 3 years after myocardial infarction. All patients recovered a normal left ventricular ejection fraction (63.3 ± 5.7%). Events and treatment during follow-up are summarized in Table 3 .
| Number of patients (%) | |
|---|---|
| Clinical events ( n = 14) | |
| Death | |
| All causes | 1 (7) |
| Cardiac causes | 0 |
| Recurrence of myocardial infarction | 0 |
| Revascularization | 0 |
| Heart failure | 0 |
| Ventricular arrhythmias | 0 |
| Stroke | 1 (7) |
| Thromboembolic events | 0 |
| Bleeding complications | 0 |
| Pharmacological treatments ( n = 12) | |
| Aspirin or clopidogrel | 11 (92) |
| Aspirin + clopidogrel | 2 (17) |
| Beta-blockers | 12 (100) |
| Angiotensin-converting enzyme inhibitors | 7 (58) |
| Statins | 12 (100) |
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