Rosa Maria Lidón

Thrombin formation and fibrinolytic activity in patients with acute myocardial infarction or unstable angina: in-hospital course and relationship with recurrent angina at rest

OBJECTIVES The goal of this study was to investigate possible differences in thrombin generation or fibrinolytic capacity in patients with unstable angina (UA) or acute myocardial infarction (AMI) with or without recurrent angina at rest. BACKGROUND Angina at rest in patients with AMI or UA is generally produced by a reduction in coronary flow, but it is unclear whether patients with or without this event differ in their thrombin generation or in their fibrinolytic capacities, which might influence the course of the culprit lesion. METHODS Thrombin-antithrombin complex (TAT), D-dimer, fibrinogen and plasminogen activator inhibitor (PAI-1) antigen plasma levels were determined in 40 patients with AMI and in 23 with UA on admission, at 10 days and at three months. RESULTS First day values for TAT, fibrinogen and D-dimer were comparable in patients with AMI and in those with UA. At 10 days they increased significantly in each group, and at 3 months they decreased to a similar extent. First day PAI-1 levels, however, were highest in both groups and declined in AMI patients at 10 days and at three months, whereas they also decreased at 10 days in UA patients but not any further at three months. Ten patients with AMI (25%) and 12 with UA (52%) developed in-hospital angina at rest. First day values for TAT, fibrinogen and D-dimer were similar in patients with or without angina, but PAI-1 levels were higher in the former subset (p < 0.008). At 10 days, however, TAT (p < 0.013) and D-dimer (p < 0.013) were higher in patients who developed angina than in those who did not. CONCLUSIONS The higher inhibition of fibrinolytic activity in the first day in patients with AMI or UA who will develop recurrent angina suggests that maintenance of a prothrombotic status may contribute to its mechanisms, perhaps by preventing passivation of the culprit thrombus/plaque. This is consistent with greater thrombin generation and greater levels of fibrynolitic products at 10 days observed in these patients compared with those who attain early stability.

High incidence of TIMI flow 0 to I in patients with ST-elevation myocardial infarction without electrocardiographic lytic criteria

BACKGROUND Most patients with ST-elevation myocardial infarction fulfilling ST-segment elevation (STE) lytic criteria present an occluded culprit artery but the occlusion rate in those with minimal STE (minSTE) not fulfilling lytic criteria is unknown. METHODS In 63 patients with minSTE (mean STE:1.2 +/- 0.6 mm) and 149 with lytic STE criteria (lyticSTE, 4.8 +/- 3.1 mm), an emergency coronary angiography was performed, serial creatine kinase-MB was determined, and ejection fraction was measured by 2-dimensional echocardiography. RESULTS The 2 groups showed similar time from pain onset to electrocardiogram (minSTE 196 +/- 199 vs lyticSTE, 176 +/- 172 min, P = .444), and although time to catheterization was longer in patients with minSTE (426 +/- 314 vs 253 +/- 239 min, P < .001), the rate of TIMI flow 0 to I (88% vs 81%, P = .21) was similar and percutaneous coronary intervention was performed in >80% of patients from the 2 groups. Moreover, patients with minSTE had higher rate of collateral circulation (27% vs 13%, P = .013), lower rate of Q waves (44% vs 60%, P = .041), lower creatine kinase-MB (202 +/- 150 vs 335 +/- 280, microg/L, P < .001), higher ejection fraction (54% +/- 9% vs 49% +/- 12%, P = .004), and lower mortality (0% vs 7.4%, P = .036). CONCLUSIONS ST-elevation myocardial infarction patients with minSTE present a high prevalence of TIMI flow 0 to I similar to those meeting lyticSTE suggesting an identical underlying mechanism and the potential to benefit from primary angioplasty.

Use of perampanel in one case of super-refractory hypoxic myoclonic status: Case report

Proper treatment of hypoxic myoclonic status is not clearly determined. Induced hypothermia is improving prognosis and a more aggressive treatment might be beneficial in some patients. Among the new options of antiepileptic drugs, perampanel (PER) is a drug with a novel mechanism, and it might be a promising drug for myoclonic status or as an antimyoclonic drug. We describe the use of PER in one patient with hypoxic super-refractory myoclonic status. Description A 51-year-old patient presented after an out-of-hospital cardiac arrest due to an acute myocardial infarction. The patient was diagnosed with clinical and electrical (EEG) myoclonic status at the rewarming phase. Several treatments were used, starting with clonazepam, valproate, sedation (midazolam, propofol), and subsequently barbiturate-induced coma with persistent myoclonic status. Finally, we decided to try PER (dose: 6–8 mg) through a nasogastric tube, resulting in a marked improvement of EEG activity and myoclonus decrease. The patient had a progressive clinical improvement, with a CPC (Cerebral Performance Category) scale score of 1. Conclusion This case shows the potential utility of PER as a therapeutic option in super-refractory hypoxic status and even its potential use before other aggressive alternatives considering their greater morbidity.

Intimal injury in a transiently occluded coronary artery increases myocardial necrosis. Effect of aspirin

This study tested the hypothesis that intimal injury in a transiently occluded coronary artery limits myocardial salvage. The effect of intimal injury on reactive hyperaemia was investigated in 17 pigs submitted to a 30-min occlusion of the left anterior descending coronary artery (LAD), not resulting in myocardial infarction. Catheter-induced intimal damage increased local platelet deposition (99mTc) and reduced hyperaemia, but did not modify myocardial platelet or polymorphonuclear leucocyte content (myeloperoxidase activity) after 6 h reperfusion. To investigate the influence of intimal injury on the extent of myocardial necrosis secondary to a more prolonged coronary occlusion, and the role of platelets on this influence, 52 pigs were submitted to a double randomization (2×2 factorial design) to 250 mg i.v. aspirin vs. placebo and to coronary intimal injury vs. no coronary damage before a 48-min occlusion of the LAD and 6 h of reperfusion. After excluding 12 animals with reocclusion, coronary intimal injury was associated with larger infarcts (triphenyltetrazolium reaction) in animals receiving placebo (36.2±7.0% of the area at risk in animals with intimal injury vs. 10.8±3.9% in animals without coronary injury, P=0.006) but not in those receiving aspirin (20.3±6.5 vs. 21.7±6.5% of the area at risk in animals with and without intimal injury respectively). These results suggest that coronary intimai injury in the reperfused artery may have adverse effects on myocardial salvage by mechanisms other than reocclusion or embolization of platelet aggregates.

Early Morning Reduction in Ischemic Threshold in Patients With Unstable Angina and Significant Coronary Disease

BACKGROUND The objective of this study was to investigate in patients with unstable angina and significant coronary stenosis (> 70%) whether or not the morning peak of myocardial ischemia is associated with a reduction in the ischemic threshold. The morning increased incidence of ischemic episodes in stable angina appears to be attributable to a coincidence of several factors. Patients with unstable angina who remain at bed rest, however, also present a similar morning increased incidence of ischemia, but its mechanisms are not completely understood. METHODS AND RESULTS The ischemic threshold was assessed by atrial pacing at 7 to 8 AM and at 12 to 1 PM in 46 patients. In the 34 with a positive pacing response (ST segment shift > 1.0 mm), ischemic threshold was lower at 7 to 8 AM than at 12 to 1 PM (131 +/- 16 versus 139 +/- 15 beats per minute, P < .001), whereas in the remaining 12 patients, the pacing response was negative. Moreover, 4 patients presented ST segment elevation during pacing in the morning but only 1 at noon and at a higher threshold. Baseline heart rate and diastolic blood pressure were higher at noon than in the morning (81 +/- 16 versus 76 +/- 13 beats per minute, P < .01, and 87 +/- 11 versus 82 +/- 10 mm Hg, P < .05). CONCLUSIONS The morning lowering of ischemic threshold in the absence of increases in baseline blood pressure or heart rate suggests that a reduced coronary vasodilator capacity or an increased coronary tone may favor the increased incidence of ischemic events during this interval.

Coincidental Annual Distribution of First and Second Acute Myocardial Infarction

••• Angiographic trials are constrained by the complex remodeling that occurs during the atherosclerotic process. 4,5 Remodeling affects the overall size of the lumen of the artery in a way that can either minimize or exaggerate the effects of true progression or regression of atheroma as perceived by the “ lumenogram”of coronary angiography. Ultrasound methods, which can distinguish arterial remodeling from atheromatous progression or regression, are theoretically more attractive for such progression/regression trials. However, this post hoc analysis, which borrows strength across baseline segments in all stenosis categories to estimate variances and thus obtain a procedure with more power, suggests that the negative, primary angiographic results of PREVENT cannot be explained solely by differences between ultrasound and coronary angiography. This significant result is found whether the more powerful statistical procedure is applied to the original data or to the augmented data containing readings from the additional interim films. With use of this approach, amlodipine may have affected coronary disease based on its effects on more significant lesions. The findings in this study should be viewed as hypothesis-generating rather than definitive proof because of the retrospective nature of this analysis. Nevertheless, the findings suggest that subtle vascular effects of amlodipine may be occurring not only in the carotid bed, but also in the coronary bed. PREVENT demonstrated an unanticipated reduction in soft, clinical end points. These events were mainly coronary events (hospitalization for unstable angina and need for percutaneous coronary intervention). Thus, the minor effects on the coronary tree noted in this study are concordant with the unanticipated benefits in the prospectively defined, secondary coronary end points. Ongoing trials, using carotid and intravascular ultrasound, will clarify whether amlodipine truly has this apparent vasculoprotective effect. In summary, posthoc analysis of angiographic data from PREVENT suggests that amlodipine has a favorable effect on the coronary tree, which is dependent on the underlying baseline stenosis. A regression effect was noted in stenoses of high baseline severity.

Lower tissue factor inhibition in patients with ST segment elevation than in patients with non ST elevation acute myocardial infarction

INTRODUCTION Mechanisms to explain the different course of coronary thrombosis between ST elevation myocardial infarction (STEMI) and non-STEMI patients remain poorly defined. We hypothesize, however, that STEMI patients may present lower tissue factor plasma inhibition to partly account for their more persistent coronary thrombotic occlusion. MATERIALS AND METHODS Total (t-TFPI ) and free tissue factor plasma inhibitor (f-TFPI), thrombin-antithrombin complex (TAT), plasminogen activator inhibitor 1 (PAI-1), von Willebrand factor (vWF), and fibrinogen were measured on admission and at 3 and 6 months in patients with a first STEMI (n:69) or non-STEMI (n:60). C reactive protein (CRP) was also measured on admission and at 3 months. RESULTS STEMI patients showed lower admission levels of t-TFPI (p=0.001), f-TFPI (p=0.030) and fibrinogen (p=0.022), and higher vWF levels (p=0.005) than non-STEMI whereas TAT, PAI and CRP levels were comparable. At 3 and 6 months VWF, t-TFPI, f-TFPI, and TAT levels declined significantly in the 2 groups (p=0.002) reaching similar values. CRP levels also declined at 3 months (p=0.002). Moreover, the rate of cardiac mortality, non fatal MI or stroke during a 6 year follow-up were unrelated to admission coagulation parameters. CONCLUSIONS The lower inhibition of tissue factor and greater endothelial dysfunction in STEMI than in non-STEMI patients may enhance thrombosis at the culprit lesion and adjacent coronary plaques, and hence, account at least in part for their different pathophysiology. This condition, however, is limited to the acute phase.

Acute cardiac syndromes without significant coronary stenosis: differential features between myocardial infarction and apical-ballooning syndrome.

ObjectiveAmong patients with acute cardiac syndromes without coronary stenosis, the clinical, electrocardiographic, echocardiographic, and angiographic features of those with a first acute myocardial infarction (AMI) were compared with those with apical-ballooning syndrome (ABS). MethodsData of consecutive patients admitted with a first AMI (n=30) or ABS (n=45) were reviewed. ResultsPatients with ABS were older (72 vs. 56 years; P=0.001) and presented a higher frequency of female sex (91 vs. 43%; P=0.001), triggering emotional or physical stress (47 vs. 17%; P=0.003) and a lower rate of tobacco smoking (27 vs. 50%; P=0.051) than those with the first AMI. They also presented a greater number of leads (5.5 vs. 3.6; P=0.01) and more anterior or anterior+inferior involvement (96 vs. 40%; P<0.001), more depressed ejection fraction (45 vs. 57%; P=0.001), more proportion of akinesia or diskinesia (89 vs. 27%; P=0.001) that extended beyond the boundaries of a single-vessel territory, and a greater rate of left ventricular outflow obstruction (29 vs. 0%; P=0.001) and heart failure (38 vs. 10%; P=0.015). Frequency of nonsignificant coronary stenosis or smooth vessels, however, was similar in both groups. ConclusionPatients with ABS were older and more frequently were women than those with first AMI without significant coronary stenosis and had larger hypocontractile areas. The preponderance of tobacco smoking, pain without triggers, and hypocontractility limited to one-vessel territory in the latter, however, may suggest a transient thrombotic/vasospastic event as their underlying mechanism as opposed to patients with ABS.

Typical angina without significant coronary stenosis: comparison of clinical profile, circadian presentation, and long-term follow-up between patients with and patients without vasospastic angina.

ObjectivesThe spectrum of patients with ‘angina and normal coronary arteries’ ranges from severe vasospasm to atypical chest pain. Among those with typical angina, however, little is known about similarities in the clinical profile and circadian presentation between typical nonvasospastic angina and normal coronary arteries (tANCA) and vasospastic angina (VA). Materials and methodsClinical, ECG, and angiographic features as well as the circadian characteristics of angina were compared between 384 tANCA and 273 VA patients. Follow-up events were also analyzed. ResultstANCA patients had greater female predominance (61 vs. 18%), higher incidence of dyspnea to moderate exertion (49 vs. 12%), lower incidence of tobacco smoking (25 vs. 67%), but a similar low rate of diabetes (8.9 vs. 4.4%). In both groups, however, dyspnea and smoking were associated with female and male sex, respectively. tANCA patients showed lower but non-negligible frequency of early morning (25 vs. 67%) and evening angina (37 vs. 54%), similar rate of nocturnal angina (47 vs. 50%), and higher rate of emotional angina (49 vs. 31%). Moreover, a high proportion of patients gained pain relief with nitroglycerin (97% in VA, 246/253, and 76% in tANCA, 231/306). At 140 months, frequent angina (>10 episodes/year) was rare (VA: 7.1% vs. tANCA: 6.3%) as was the rate of cardiac death/myocardial infarction (7.3 vs. 6.0%, P=0.524). ConclusionDespite differences in the clinical profile between VA and tANCA patients, there is notable sharing of circadian presentation of rest angina, response to nitroglycerin, and long-term presence and frequency of angina that suggests more similarities in underlying mechanisms than heretofore suspected.

Left ventricular dynamic gradient and pericardial effusion. A life threatening combination in patients with apical ballooning syndrome

mortality in patients with acute myocardial infarction. Korean Circ J 2010;40: 616–24. [5] Durgan DJ, Pulinilkunnil T, Villegas-Montoya C, et al. Short communication: ischemia/ reperfusion tolerance is time-of-day-dependent: mediation by the cardiomyocyte circadian clock. Circ Res 2010;106:546–50. [6] Kim W, Park HH, Park CS, et al. Impaired endothelial function in medical personnel working sequential night shifts. Int J Cardiol 2011;151: 377–8. [7] Barion A. Circadian rhythm sleep disorders. Dis Mon 2011;57:423–37.