Troponin for the estimation of infarct size: what have we learned?

In acute myocardial infarction (AMI), the extent of myocardial damage is closely linked to prognosis. Early determination of infarct size is therefore key to assessing the future risk of patients and instructive for optimization of therapeutic strategies. The cardiac troponins, by allowing the physician to track the extent of injury suffered by the myocardium, provide a window into the heart. This article addresses the relationship between the cardiac troponins and the infarct size in AMI. Taken together, the data suggest that the cardiac troponins provide very useful information in this respect and especially in patients with ST elevation myocardial infarction. More studies are needed to understand how cardiac troponin-estimated infarct size may be integrated with other prognostic assessments and employed systematically in risk stratification. Early data are promising and indicate that cardiac troponins could provide useful information for early risk assessment that is complementary to the determination of cardiac function and volumes.     

Late opening of the infarct related artery: an open or shut case?

Is there a place for the late opening of infarct related arteries, beyond the time window for myocardial salvage?     

Myocardial infarct with ST segment depression: an absolute contraindication to thrombolytic therapy?]

The benefit of thrombolytic reperfusion has been demonstrated widely in patients who present with ST segment elevation and develop myocardial infarction. Instead, the role of thrombolytic therapy in patients who present with ST segment depression and develop myocardial infarction is still unresolved. The purpose of this paper is to review the literature on the subject and give rise to reconsideration of thrombolytic therapy in this subgroup of patients who are usually excluded from receiving thrombolytic agents because of the absence of indications and the presence of contraindications.     

Chlamydia pneumoniae and myocardial infarct? (Serologic study)

At disposal for tests were 156 blood sera collected from patients with acute myocardial infarction (AMI samples) and 67 blood sera collected from control persons. The sera were tested by the following reactions: complement fixation test (CFT) with genus-specific antigen (C. psittaci, Bioveta, Ivanovice na Hané), ELISA in the immunoglobulin classes IgG and IgA using the MOMP (Vircell, Spain) and LPS (MEDAC, Hamburg, BRD) Chlamydia pneumoniae (C. p.) antigens, and indirect immunofluorescence test with MOMP C. p. antigen (MRL Diagnostics, USA). Eight AMI samples were not tested by CFT owing to haemolyis or lipaemia. CFT titres ranging from 1:4 to 1:16 were found in 28 of the 148 AMI samples (18.9%) and 3 of the 67 control samples (4.5%). The between-group difference was highly significant (chi 2 = 7.795 at 0.01). Positive by rELISA anti LPS C. p. were 89 of the 155 AMI samples (57%) and 22 of the 62 control samples (35%). Also this difference was highly significant (chi 2 = 8.528; alpha = 1%). The following conclusions can be drawn from the results: 1. Chlamydia pneumoniae can play an important role in the aetiology of atherosclerosis leading to AMI. 2. rELISA anti-LPS can be recommended for routine serological diagnostics of C. pneumoniae and studies of its role in the aetiology of atherosclerosis. 3. The complement fixation test is still suitable for the screening of human chlamydiosis.     

Limitation of myocardial infarct size after primary angioplasty: is a higher patency the only mechanism?

BACKGROUND: Several studies demonstrate a better outcome after primary angioplasty compared with thrombolysis. The mechanism is assumed to be a higher rate of open infarct-related vessels. METHODS AND RESULTS: We conducted a randomized trial of primary coronary angioplasty compared with thrombolysis. A total of 401 patients with acute myocardial infarction were randomly assigned to either primary angioplasty or thrombolytic therapy. Radionuclide left ventricular ejection fraction was performed before hospital discharge. Infarct size was estimated by measurement of serial lactate dehydrogenase activity (LDH Q72). Separate analyses were performed in patients with an open infarct-related vessel, either after thrombolysis or angioplasty. Baseline characteristics were comparable between the 2 treatment groups. Of the 197 patients treated with angioplasty, 176 (89%) had an open infarct-related vessel compared with 126 (62%) of the 204 patients treated with thrombolysis (P <.001). In patients with an open infarct-related vessel, those treated with primary angioplasty had a lower enzyme release compared with those treated with thrombolysis: LDH Q72 949 (748) and 1200 (1117), respectively (P <.05). Compared with angioplasty, patients treated with thrombolysis had a lower left ventricular ejection fraction. In the subgroup of patients with an open infarct-related vessel, after thrombolysis or angioplasty, patients treated with thrombolysis still had a lower ejection fraction (47% vs 50%, P <.05). Multivariate analysis, adjusting for differences in several clinical variables, did not change these results. Patients with an open infarct-related vessel and thrombolysis had a higher risk of an ejection fraction <40% compared with patients treated with primary angioplasty (relative risk 1.9, 95% confidence interval 1.0 to 2.7). CONCLUSIONS: Despite successful thrombolysis, with sustained patency of the infarct-related vessel, primary angioplasty remains superior to thrombolytic therapy with regard to left ventricular function and enzymatic infarct size. This may be caused by adverse effects of fibrinolytics on infarcted myocardium.     

Pioglitazone limits myocardial infarct size,activates Akt,and upregulates cPLA2 and COX-2 in a PPAR-γ-independent manner

Pioglitazone (PIO), a PPAR-γ agonist, limits myocardial infarct size by activating Akt and upregulating cytosolic phospholipase A₂ (cPLA₂) and cyclooxygenase (COX)-2. However, PIO has several PPAR-γ-independent effects. We assessed whether PIO limits myocardial infarct size in PPAR-γ–knockout mice, attenuates hypoxia-reoxygenation injury and upregulates P-Akt, cPLA₂, and COX-2 expression in PPAR-γ–knockout cardiomyocytes. Cardiac-specific inducible PPAR-γ knockout mice were generated by crossing αMHC-Cre mice to PPAR-γ^loxp/loxp mice. PPAR-γ deletion was achieved after 7 days of intraperitoneal tamoxifen (20 mg/kg/day) administration. Mice received PIO (10 mg/kg/day), or vehicle, for 3 days and underwent coronary occlusion (30 min) followed by reperfusion (4 h). We assessed the area at risk by blue dye and infarct size by TTC. Cultured adult cardiomyocytes of PPAR-γ^{loxp/loxp/cre} mice without or with pretreatment with tamoxifen were incubated with or without PIO and subjected to 2 h hypoxia/2 h reoxygenation. Cardiac-specific PPAR-γ knockout significantly increased infarct size. PIO reduced infarct size by 51% in PPAR-γ knockout mice and by 55% in mice with intact PPAR-γ. Deleting the PPAR-γ gene increased cell death in vitro. PIO reduced cell death in cells with and without intact PPAR-γ. PIO similarly increased myocardial Ser-473 P-Akt, cPLA₂, and COX-2 levels after hypoxia/reoxygenation in cells with and without intact PPAR-γ. PIO limited infarct size in mice in a PPAR-γ-independent manner. PIO activated Akt, increased the expression of cPLA₂ and COX-2, and protected adult cardiomyocytes against the effects of hypoxia/reoxygenation independent of PPAR-γ activation.     

Extensive haemorrhagic transformation of infarct: might it be an important cause of primary intracerebral haemorrhage?

Data from prior studies using serial imaging and post mortem data support the possibility that at least some cases of apparent primary intracerebral haemorrhage are due to early haemorrhagic transformation of infarct. If some primary intracerabral haemorrhage is actually early haemorrhagic transformation of infarct, then secondary stroke prevention for ischaemic stroke might be appropriate and so future studies should obtain data to determine the frequency of early major haemorrhagic transformation of infarct.     

Does sleep apnea increase the risk of myocardial infarct during sleep?]

Myocardial infarction shows a circadian pattern with a maximum in the early morning hours. In patients with sleep-related breathing disorders (SRBD), it is assumed that apnea-associated changes of hemodynamics, blood gases, and rheology lead to a higher frequency of myocardial infarction during sleep. This investigation analyzes the circadian pattern of myocardial infarction in patients with and without SRBD. Within a time period of 20 months, 89 male patients with acute myocardial infarction were consecutively admitted to the intensive care unit. A nocturnal long-term registration of oxygen saturation, heart rate, breathing sounds, and body position by means of a 4-channel recording system (MESAM IV) was carried out in 59 of the 89 patients 6 to 10 days (evaluation I) and in 43 of 59 patients 22 to 28 days after infarction (evaluation II). Sleep apnea with a respiratory-disturbance-index (RDI > or = 10/h was found in 44.1/39.5% of the patients (evaluation I/II). In 22% of the patients, time of infarction was during a sleeping period. Patients with myocardial infarction during sleep had a clearly higher RDI in comparison to patients with a myocardial infarction during wakefulness (evaluation I: 22.7 versus 9.4/h; p = 0.08; evaluation II: 20.3 versus 7.3; p < 0.05). 53.6% of all myocardial infarctions occurred during the time period 5:00-11:00 a.m. Investigations in a larger number of patients are necessary to confirm these results as well as the relevance of sleep apnea as a cardiovascular risk factor.     

Protecting the acutely ischemic myocardium beyond reperfusion therapies: are we any closer to realizing the dream of infarct size elimination?

Patients currently treated for acute myocardial infarction receive reperfusion therapy as their only anti-infarct intervention. Although pharmacologic agents have been evaluated in the past for their ability to salvage ischemic myocardium when administered at reperfusion, until very recently none has demonstrated clear efficacy in clinical trials. However, a new generation of interventions has emerged which protects the heart by activating the reperfusion-induced salvage kinase (RISK) pathway. Unlike the disappointing results documented with previously touted putative cardioprotective agents, the preclinical experience with these newer interventions is very consistent indicating that there is a high likelihood that they will be effective clinically. Ischemic postconditioning, which also acts by activating the RISK pathway, has shown marked reduction in infarct size in small-scale trials. Finally, if a strategy for rapidly cooling the heart can be devised so that the in-hospital normothermic ischemic time can be significantly reduced, then infarct size can be even further decreased. In our opinion it is well within our reach using existing technologies to see the day when infarction can be virtually eliminated in the patient with acute coronary occlusion.