Post Infarction Research Articles

Apport de l’IRM cardiaque à l’exploration des cardiopathies ischémiques

This article presents the current and future possibilities of the cardiac magnetic resonance imaging (MRI) in the ischemic heart disease. It is not an emergency technique, but is becoming an element of decision for an acute myocardial infarction. It makes it possible to visualize the extent of the myocardial lesions in post acute infarction, to appreciate functional recovery and to uncover a nonsymptomatic coronary stenosis or of atypical clinical presentation. The visualization of the coronary arteries in MRI is realizable, but remains experimentation field. The cardiac MRI place is to be defined by each medical team according to their diagram of ischemic heart disease follow-up.

Abstract 1342: The NF-kappaB P50 Subunit Protects Against Remodeling and Cardiac Dysfunction Following Myocardial Infarction

Introduction Left ventricular (LV) remodeling leads to congestive heart failure and is a main determinant of morbidity and mortality following myocardial infarction (MI). To further improve the treatment of post infarct LV remodeling, a better understanding of the molecular mechanisms involved in this complicated process is required. The nuclear factor (NF)- κB family (p50, p52, p65) usually forms dimers that regulate DNA transcription in response to a variety of stimuli including pro-inflammatory cytokines, oxidative stress and also ischemia. Inhibition of NF- κB has been shown to reduce heart failure following MI in rats. The specific role of the different NF- κB subunits during LV remodeling, however, has not been clarified thus far. In this study, we elucidate the role of the NF- κB p50 subunit in post infarct LV remodeling. Methods and Results MI was induced in wild type C57Bl6 mice and NF- κB p50 KO mice. Without affecting infarct size (45.4 ± 4.3 vs. 42.5 ± 4.6%; p=0.461), the absence of NF- κB p50 increased the extent of LV remodeling (EDV: 175 ± 13 vs. 107 ± 11 μl; p=0.005) and aggravated systolic dysfunction (LVEF: 16.1 ± 1.5 % vs. 24.7 ± 3.7%; p=0.045) 28 days following MI as assessed by magnetic resonance imaging (9.4 T). In the non-infarcted myocardium, interstitial fibrosis (1.53 ± 0.28 vs. 1.05 ± 0.15 grayvalue/μm 2 ; p=0.042) and hypertrophy (426 ± 51 vs. 251 ± 12 μm 2 /cardiomyocyte; p=0.018) were increased in NF-κB p50 KO mice. In the infarct area, however, collagen density was decreased (15.11 ± 1.16 vs. 27.28 ± 4.93 grayvalue/μm 2 ; p=0.028), which was accompanied by increased TNF-alpha mRNA expression (0.086 ± 0.04 vs. 0.026 ± 0.015; p=0.046) and increased MMP9 activity (0.31 ± 0.03 vs. 0.19 ± 0.03; p=0.049) Conclusion These data provide evidence for a protective role of NF- κB p50 in post infarct maladaptive LV remodeling, most likely by reducing inflammatory cytokine production and matrix degradation.

Abstract 408: Thioredoxin-1 Gene Delivery Induces Hemeoxygenase-1 Mediated Myocardial Preservation after Chronic Infarction in Spontaneously Hypertensive Rats

Hypertension the major risk factor for many cardiovascular diseases is a result of multiple causes along with excessive generation of reactive oxygen species resulting in imbalance of redox status. Thioredoxin-1 (Trx-1) is a redox regulatory multifunctional protein with anti-inflammatory, anti-apoptotic and antioxidant effects. In the present study we investigated the therapeutic potential of Adeno-Trx-1 in spontaneously hypertensive rats (SHR). The rats were assigned to four different groups (n = 24) such as (1) normotensive Wistar Kyoto (WKY) (2) SHR (3) SHR +Adeno-Lac-Z (SHRLac-Z) and (4) SHR +Adeno-Trx-1 (SHRTrx-1). Echo-guided gene delivery to the anterior wall of left ventricle was performed using 1x109 pfu of adenovirus constructed with Trx-1 and Lac-Z. Two days after injection of adeno virus, the hearts were subjected to permanent left anterior descending coronary artery occlusion (MI). Left ventricular functions by Echocardiography were examined after 30 days of MI as the significant changes in left ventricle were observed after 4 weeks of MI. Decreased left ventricular inner diameter (7 vs 9 mm) and increased ejection fraction (52 vs 42 %), fractional shortening (28 vs 22 %) was observed in SHRTrx-1 compared to SHR. Infarct size, cardiomyocyte apoptosis and protein expression profiles (by Confocal and Western blot analysis) were observed at predetermined time points i.e after 24 and 48 hours of MI respectively. Decreased infarct size (52% vs 67%), cardiomyocyte apoptosis by TUNEL assay (161 vs 240) and increased expression of Trx-1 and HO-1 were observed in SHRTrx-1 compared to SHR. Confocal results were also confirmed by Western blot analysis. Results documented increased expression of Trx-1 (1.8 fold) and HO-1 (1.4 fold) in SHRTrx-1 as compared to SHR. In addition, we have also observed increased expression of anti-apoptotic protein Bcl-2 (1.7 fold) in SHRTrx-1 treated group compared SHR. Thus our results demonstrate for the first time that the cardioprotective effect of Adeno-Trx-1 therapy in SHR is Trx-1/HO-1/Bcl-2 mediated and may represent a novel mechanism for therapy against hypertension induced post infarction heart failure.

Management of blood pressure after acute ischemic stroke: An evidence‐based guide for the hospitalist

Hospitalists are frequently called upon to manage blood pressure after acute ischemic stroke. A review of both post infarction cerebral perfusion physiology and the data from randomized trials of antihypertensive therapy is necessary to explain why consensus guidelines for blood pressure management after stroke differ from those of other hypertensive emergencies. The peri-infarct penumbra is the central concept in understanding post ischemic cerebral perfusion. This area of impaired cerebral blood flow is dependent on mean arterial blood pressure and acute reduction of blood pressure may expand the area of infarction. Review of clinical trials fails to show benefit from reduction of blood pressure after ischemic stroke and current guidelines suggest antihypertensive therapy be employed if the systemic blood pressure is greater than 180/105 mmHg after tPA is employed, or 220/120 mmHg when tPA is not used. Induced hypertension remains a promising but unproven therapy in the acute setting, but the evidence for long term control of blood pressure to less than 140/80 mmHG for secondary prevention of stroke is strong. Adherence to guidelines is poor but it is recognized that current evidence is limited by a lack of trials in which blood pressure is titrated to a pre-specified goal, as is common in clinical practice.

Attenuation of ischemia reperfusion injury in failing hearts by endothelin-a receptor blockade

Objective: Ischemia/reperfusion (I/R) injury due to cardioplegic arrest is a problem in patients with reduced LV function. We investigated the effect of chronic versus acute administration of the selective endothelin-A receptor antagonist TBC-3214Na during I/R in failing hearts. Methods: Male SD rats underwent coronary ligation. 3 days post infarction group 1 (n=11) was administered TBC-3214Na continuously with their drinking water, group 2 and 3 received placebo. 7 weeks post infarction hearts were evaluated on a blood perfused working heart during 60′ ischemia and 30′ reperfusion. In group 2 (n=10) TBC-3214Na and in group 3 placebo were added to cardioplegia during ischemia. Data: At similar infarct size postischemic recovery of cardiac output (group1: 91±10%, group2: 86±11% vs. placebo: 52±15%; p<0,05) and external heart work (group1: 90±10%, group2: 85±13% vs. placebo: 51±17%, p<0,05) was significantly enhanced in group 1+2 while recovery of coronary flow was only improved in group 2 (group2: 121±23% vs. group1: 75±13%, placebo: 64±15%, p<0,05). In group 2 myocardial oxygen delivery and high energy phosphates were enhanced accompanied by a lower lactate production, and transmission electron microscopy revealed less ultrastructural damage. Conclusion: Ultrastructural and biochemical evaluation indicates an improvement in capillary perfusion only under acute TBC-3214Na administration during ischemia/reperfusion resulting in a better cardiac function post ischemia.

CT17P IMAGES OF AN INFARCT RELATED INCOMPLETE LEFT VENTRICULAR RUPTURE MANAGED WITH PERICARDIAL PATCH REPAIR

Introduction A 54‐year‐old woman presented with an inferior MI &amp; post infarction pericarditis. Incomplete LV rupture was confirmed by MRI. She was managed with pericardial patch repair of her LV.Case Our patient presented with 1 week of chest pain, elevated Troponin T &amp; ECG suggesting a recent inferior MI. Angiography showed an occluded obtuse marginal artery, left ventriculogram a 1 cm endocardial defect in a hypokinetic segment of the infero‐lateral LV &amp; transthoracic echo a small LV wall defect with a haemodynamically insignificant pericardial effusion. Cardiac MRI confirmed an infero‐lateral infarct &amp; an anatomical defect suggesting incomplete rupture of the LV free wall. Operatively straw colored pericardial fluid &amp; a shaggy pericarditis were noted. Myocardium supplied by the obtuse marginal artery had appearances of recent infarction &amp; on cardiopulmonary bypass a pericardial patch was glued over this area. The patient required elective drainage of a persistent pericardial effusion and was discharged on the 13th post‐operative day. 4 weeks after discharge she was asymptomatic with echo showing a resolving pericardial effusion.Discussion Incomplete LV rupture following MI is rare &amp; caused by haemorrhagic dissection of the ventricular wall leaving a defect lined by epicardium alone. The natural history is not well described but may include free wall rupture with an in‐hospital mortality of 70%. Pericardial patch augmentation of the LV may reduce the risk of free wall rupture.Conclusion Management of incomplete LV rupture is poorly described but reinforcement of the area with a pericardial patch may be performed safely to reduce the risk of free wall rupture.

8.26

8.26

Financial, family, and social factors impacting on cardiac rehabilitation attendance

Attendance in phase 2 cardiac rehabilitation program after acute myocardial infarction is poor. To identify and explore the demographic factors that influence peoples' decisions to attend cardiac rehabilitation programs. A descriptive-interpretive design was used. Semi-structured interviews were conducted with 10 people post infarction in Victoria, Australia after their first scheduled appointment to attend outpatient cardiac rehabilitation. The interview transcripts were thematically analysed. The perceived relevance of cardiac rehabilitation related to the context of people's lives, namely their financial, family and social situation, and how important program outcomes were seen to be relevant to this context. The findings of this study suggest that there are a proportion of people unlikely to attend outpatient cardiac rehabilitation programs following an AMI despite encouragement to attend. It may be unrealistic to aim for 100% referral and uptake into cardiac rehabilitation programs and therefore an inappropriate endpoint by which to evaluate such programs.

Acute decrease of left ventricular mechanical dyssynchrony and improvement of contractile state after left ventricular restoration

Objective: Surgical left ventricular restoration (SVR) by means of endoventricular patch aneurysmectomy in patients with post infarction aneurysm should result in acutely improved left ventricular performance. This study tests the capacity of geometric rebuilding by SVR to reconstitute a more synchronous and synergic contractile pattern.

Transplantation of embryonic cardiomyocytes reduces post infarct cardiac arrhythmias in mouse

Introduction: First clinical studies show an increased incidence of ventricular arrhythmias after intramyocardial transplantation of skeletal myoblasts (SMB). We therefore determined the electrical vulnerability of intact and infarcted hearts with or without cellular cardiomyoplasty using electrophysiological investigation (EPI) in vivo.

Biomarkers of Cardiovascular Damage and Dysfunction—An Overview

Acute coronary syndromes (ACS) are due to the rupture or erosion of atheromatous plaques. This produces, depending on plaque size, vascular anatomy and degree of collateral circulation, progressive tissue ischaemia which may progress to cardiomyocyte necrosis and subsequent cardiac remodelling. Cardiac biomarkers can be used for diagnosis and assessment of all of these stages. Markers to detect myocardial ischaemia at the pre-infarction stage are potentially the most interesting but also the most challenging. An ischaemia marker offers the opportunity to intervene to prevent progression to infarction. The challenges with potential ischaemia markers are specificity and the diagnostic reference standard for assessment. To date, only one, ischaemia modified albumin, has reached the point where clinical studies can be performed. The measurement of the cardiac troponins, cardiac troponin T and cardiac troponin I, has become the diagnostic standard as the biomarker of myocardial necrosis. The sensitive nature of troponin measurement has also revealed that myocardial necrosis is also found in a range of other clinical situations. This illustrates the need to use all clinical information for diagnosis of acute myocardial infarction. The measurement of B type natriuretic peptides can be shown to be diagnostic and prognostic for both acute ACS and detecting the sequelae of post infarction myocardial insufficiency. The role of the B type natriuretic peptides in detection of cardiac failure, acute and chronic, is well defined. Their role in ACS remains the subject of further studies.

Transcatheter closure of ischemic and post‐traumatic ventricular septal ruptures

Post-traumatic ventricular septal defects (VSD) can occur after acute MI or iatrogenically after invasive surgical procedures. Emergency surgery is associated with high perioperative mortality and postsurgical shunt in up to 20% of patients. Transcatheter closure (TCC) of post MI VSD may be an alternative that avoids the high risk of surgery. We report a lower mortality and morbidity than surgical closure in the post infarction VSD's even with a short interval between defect occurrence and percutaneous device placement. Furthermore, in patients with a failed or suboptimal surgical result adjunctive percutaneous closure may be beneficial and offers an alternative to redo VSD repair. Finally, in patients who suffer an unexpected traumatic VSD post surgical procedure, percutaneous closure offers an alternative with excellent results.

Atherosclerosis, inflammation, leukocyte function and the effect of statins

Atherosclerosis, inflammation, leukocyte function and the effect of statins

Reply to “Ventricular remodelling following acute myocardial infarction: The role of altered collagen homeostasis"

We agree with Turhan and colleagues that the results from our clinical observational study are consistent with other works on collagen metabolism following infarction [1]. They highlight the importance of matrix metalloproteinase (MMP) activity in collagen homeostasis. While we agree that MMPs strongly influence collagen and matrix activity, attempts to attenuate this process have yielded conflicting results. Indeed, Hudson et al. recently reported that selective MMP inhibition fails to reduce LV remodeling post infarction [2]. We believe that this illustrates the complexity of the relationship between the MMP/TIMP system and collagen homeostasis. Turhan and colleagues criticise the “heterogenous study groups”, but this was a “real world” study, examining patients presenting early with typical presentation of myocardial infarction and ECG criteria for thrombolysis. The fact that the findings remain robust despite this heterogeneity supports the utility of serological markers of collagen metabolism in identifying those at risk of remodeling. We chose wall motion index as a dichotomous variable due to the fact that this is a powerful predictor of subsequent remodeling and mortality [3], rather than dividing the patients by site of infarct. However, we agree that anterior infarction is likely to be associated with abnormal wall motion and increased CITP and indeed, our study supports this (there were more anterior infarcts in the abnormal wall motion group 39% vs. 18%). Turhan and colleagues also state that it is not possible to see normal wall motion index

Neurohumoral Changes in Patients With Left Ventricular Dysfunction Following Acute Myocardial Infarction and the Effect of Nitrate Therapy: A Randomized, Double-Blind, Placebo-Controlled Long-Term Study

Several neurohumoral mechanisms involved in cardiovascular regulation are activated in the failing heart, but only limited information is available regarding the influence of long-term nitrate therapy. This was a double-blind, randomized comparison of isosorbide-5-mononitrate (IS-5-MN), 60 mg given orally, once daily for 11 months to patients (n = 47) with left ventricular (LV) dysfunction following acute myocardial infarction (AMI). Forty-five patients received placebo. All patients received ramipril.Plasma natriuretic peptides (atrial [ANP] and brain [BNP] natriuretic peptide), epinephrine, norepinephrine (NEPI), antidiuretic hormone, aldosterone (Aldo), renin activity (PRA), substance P, neuropeptide Y-like immunoreactivity, calcitonin gene-related peptide, and vasoactive intestinal peptide were measured at baseline and at the end of the treatment period. Clinical, echocardiographic, and hemodynamic data were also obtained. Chronic nitrate therapy does not significantly affect the neurohumoral status in patients with LV dysfunction after AMI, apart from a decrease in ANP. Some hormones are more closely associated with diastolic dysfunction/increased volume load (ANP and BNP) and others are more closely associated with systolic dysfunction (PRA, NEPI, Aldo). There is a temporal dissociation of these 2 groups of hormones 1 year post infarction: ANP and BNP decrease, whereas NEPI and Aldo show a slight increase. BNP levels do not reflect all important pathophysiologic mechanisms in heart failure. Consequently, the use of other neurohormonal factors than BNP for monitoring of heart failure therapy should be explored.

Cell‐Free DNA Levels as a Prognostic Marker in Acute Myocardial Infarction

Cell-free DNA that originates from cell death, circulates in peripheral blood. There are indications that the infarcted myocardium contributes to an increase of cell-free DNA levels. Our aims were to quantify levels of cell-free DNA in patients with acute myocardial infarction (AMI) and examine their correlation with myocardial markers and with postinfarction (PI) clinical course. Thirteen patients (age 57 +/- 16 year) admitted with AMI and who underwent thrombolysis with reteplase within 6 h from the onset of chest pain were studied. PB samples were collected on admission and for 5 consecutive days. Creatine kinase (CK) and troponin I (TnI) were measured on admission and every 8 h for 3 consecutive days. Clinical events were recorded throughout the hospitalization period. Cell-free DNA levels were also measured in 30 healthy controls. Log-transformed mean (+/-SE) of maximum free DNA values in patients higher than controls (6873 +/- 357 g.e./mL verses 4112 +/- 234 g.e./mL, P < 0.0001). Log-transformed maximum values of CK and TnI were correlated with log-transformed free DNA values of first (r = 0.62, P = 0.02/r = 0.68, P = 0.01) and second (r = 0.57, P = 0.04/r = 0.72, P = 0.0053) PI day. Nine patients (group A) had an uncomplicated PI clinical course and four patients (group B) had recorded events (three with angina and one death). Free DNA levels on the second PI day were higher in group B than group A (1298.0 +/- 796.0 g.e./mL verses 244.6 +/- 257.7 g.e./mL, P = 0.003). In conclusion, free DNA levels are significantly higher in patients with AMI than in controls and may play a role in the prognosis of these patients.

Medifile drug Information bulletin

The recent publication of the Perindopril Remodeling in Elderly with Acute Myocardial Infarction (PREAMI) study showed that perindopril significantly reduced the composite risk of death, hospitalisation for heart failure, and cardiac remodeling in an elderly population with preserved left ventricular (LV) function, following an acute myocardial infarction. In light of this trial, this edition of the Medifile reviews the process of cardiac remodelling post infarction, with specific focus on the role of the Renin-Angiotensin-Aldosterone System (RAAS). The results and clinical significance of PREAMI are then reviewed and discussed. More....

Repair of Postinfarction Ventricular Septal Defect Through the Right Atrium

Repair of post infarction posterior ventricular septal defect has generally been performed with a ventriculotomy through the infarcted zone. This approach has a significant mortality and morbidity due to haemorrhage, extension of infarction or further compromise of ventricular function secondary to suture placement. We present a case with delayed repair of a post infarction posterior septal defect using a right atrial approach, where no discrete infarct or other abnormality of the free ventricular wall was found.

Post-infaction ventricular septal defect in Nairobi: case report

Post infarction ventricular septal defect results from perforation of the ventricular septum secondary to ischaemic injury following myocardial infarction. Ischaemic heart disease till recently was thought to be an uncommon disease in this part of the world, but now more and more cases are being seen as a result of the changes in thelife styles of the population in this country and in the developing world in general. This is a case report of the first case of post infarction ventricular septal defect presenting to surgery for repair in this country.

P1-54: Correlation between CARTO endocardial mapping and MRI with Gadolinium delayed enhancement for the definition of myocardial scar in patients with ventricular tachycardia and chronic myocardial infarction

Sinus Rhythm (SR) Radiofrequency Ablation is often the only possibility to cure the post infarction ventricular tachycardia (VT) due to intolerable or unstable circuits. The magnetic resonance imaging (MRI) data, in addition to the left ventricle (LV) Sinus Rhythm mapping can helps to precise the ablation strategy in order to obtain an optimal result.