Chronic Anterior Myocardial Infarction Research Articles

A pilgrim seeking diagnosis

We present the case of an unusual presentation of Dressler’s syndrome and the important role of new imaging techniques in its diagnosis. A 42-year-old man was admitted with progressive dyspnoea and pleuritic chest pain during the last two months. Physical examination showed signs of hemodynamic instability (BP 75/40, HR 120 bpm). X-Ray showed cardiomegaly and electrocardiogram was suggestive of chronic anterior myocardial infarction. Transthoracic echocardiography showed pericardial effusion with signs of hemodynamic compromise. Emergent cardiac surgery was performed with suspicion of cardiac rupture. Only fibrinous material and serous fluid was found. 72 hours later he required reoperation because of recurrence of cardiac tamponade. Pleuropericardial window was made. Anti-inflammatory treatment was initiated. At discharge a magnetic resonance imaging study was performed. Diffuse pericardial inflammation consistent with a diagnosis of Dressler’s syndrome (DS) was demonstrated in T2- weighted black-blood and late enhancement sequences. One month later neither pleural nor pericardial effusion had recurred. Postinfarction pericardial effusions are common and magnetic resonance imaging has proven useful in determining its aetiology.

Functional Recovery Following Intracoronary Infusion of Autologous Mononuclear Bone Marrow Cells in Patients With Chronic Anterior Myocardial Infarction and Severely Depressed Ventricular Function

Studies have shown that intracoronary infusion of mononuclear bone marrow cells improves ventricular function in patients with acute myocardial infarction. However, less information is available about the use of this therapy during the chronic phase of a myocardial infarction. This study involved an analysis of the clinical, echocardiographic and angiographic changes observed in 19 patients with a revascularized chronic anterior myocardial infarction and depressed ventricular function who were treated by cell therapy. A series of patients were monitored during treatment and 6 months and 1 year after treatment. Autologous bone marrow was obtained by needle aspiration of the iliac crest and mononuclear cells were isolated by density-gradient centrifugation. An in vitro biological study of a sample of the infused cells was performed using fluorocytometry, phenotype marking and an analysis of the chemotactic properties of the cells. Six months and 1 year after cell therapy, a modest improvement was observed in clinical status and ventricular function, which was most pronounced in the group of patients who responded. Characteristically, these patients were revascularized close to the time of cell therapy. There was an inverse relationship between functional recovery and biological parameters that reflected a state conducive to cell migration. The intracoronary infusion of mononuclear bone marrow cells into patients with chronic anterior myocardial infarction appeared to result in a modest clinical and functional improvement after 6 months which was sustained up to 1 year after treatment.

P-131 Mitral Regurgitation in Chronic Anterior Myocardial Infarction: Results Following Surgical Ventricular Restoration and Mitral Repair

P-131 Mitral Regurgitation in Chronic Anterior Myocardial Infarction: Results Following Surgical Ventricular Restoration and Mitral Repair

Determinants of Ischemic Mitral Regurgitation in Patients with Chronic Anterior Wall Myocardial Infarction: A Real Time Three‐Dimensional Echocardiography Study

We sought to elucidate the geometric determinants of ischemic mitral regurgitation (IMR) in patients with chronic anterior myocardial infarction (MI). In 16 patients with anterior MI only (Group A) and 18 patients with both anterior and inferoposterior MI (Group B), three parallel equidistant anteroposterior (AP) planes (medial, central, lateral) perpendicular to the mitral valvular commissure-commissure plane were generated. The systolic tenting area of the mitral valve (MVTa) and the angles between the annular plane and leaflets (anterior, Aalpha; posterior, Palpha) on the AP planes were measured. The left ventricular end-systolic and end-diastolic volumes, and end-diastolic and end-systolic mitral annular area (MAAs) were obtained. The regurgitant orifice area (ROA) was significantly smaller in Group A than Group B (0.08 +/- 0.09 vs 0.20 +/- 0.18 cm(2), P < 0.05). In the total of 34 patients, the medial MVTa (P < 0.001), MAAs (P < 0.05) and the spherical index (P < 0.05) were three independent determinants of ROA while the left ventricular volumes were not. MAAs was the only independent determinant of ROA in Group A, while the medial MVTa was in Group B. Palpha (P < 0.05) and MVTa (P = 0.06) tended to be larger in the medial than the lateral side in Group B, while no differences were found in Group A. The geometry of the mitral valve apparatus was more important than the left ventricular volumes in determining the severity of IMR in patients with anterior MI. The posteromedial side tenting could play a critical role in causing significant IMR when the inferoposterior MI coexists with anterior MI.

Female Mice Lacking Estrogen Receptor β Display Prolonged Ventricular Repolarization and Reduced Ventricular Automaticity After Myocardial Infarction

Major gender-based differences in the incidence of ventricular tachyarrhythmia after myocardial infarction have been shown in humans. Although the underlying mechanisms are unclear, earlier studies suggest that estrogen receptor-mediated effects play a major role in this process. We examined the effect of estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta) on the electrophysiological phenotype in female mice with and without chronic anterior myocardial infarction. There was no significant difference in overall mortality, infarct size, and parameters of left ventricular remodeling when we compared infarcted ERalpha-deficient and ERbeta-deficient mice with infarcted wild-type animals. In the 12-hour telemetric ECG recording 6 weeks after myocardial infarction, surface ECG parameters did not show significant differences in comparisons of ERalpha-deficient mice versus wild-type controls, infarcted versus noninfarcted ERalpha-deficient mice, and infarcted ERalpha-deficient versus infarcted wild-type mice. However, infarcted ERbeta-deficient versus noninfarcted ERbeta-deficient mice showed a significant prolongation of the QT (61+/-6 versus 48+/-8 ms; P<0.05) and QTc intervals (61+/-7 versus 51+/-9 ms; P<0.05) and the JT (42+/-6 versus 31+/-4 ms; P<0.05) and JTc intervals (42+/-7 versus 33+/-4 ms; P<0.05). Furthermore, infarcted ERbeta-deficient versus infarcted wild-type mice showed a significant prolongation of the QT (61+/-6 versus 53+/-8 ms; P<0.05) and QTc intervals (61+/-7 versus 53+/-7 ms; P<0.05) and the JT (42+/-6 versus 31+/-5 ms; P<0.05) and JTc intervals (42+/-7 versus 31+/-5 ms; P<0.05), accompanied by a significant decrease of ventricular premature beats (7+/-21/h versus 71+/-110/h; P<0.05). Finally, real-time polymerase chain reaction-based quantitative analysis of mRNA levels showed a significantly lower expression of Kv4.3 (coding for I(to)) in ERbeta-deficient mice (P<0.05). Estrogen receptor beta deficiency results in prolonged ventricular repolarization and decreased ventricular automaticity in female mice with chronic myocardial infarction.

Increased Mortality and Aggravation of Heart Failure in Estrogen Receptor-β Knockout Mice After Myocardial Infarction

Lower mortality rates among women with chronic heart failure than among men may depend in part on the action of female sex hormones, especially estrogens. The biological effects of estrogens are mediated by 2 distinct estrogen receptor (ER) subtypes (ERalpha and ERbeta). The present study was undertaken to determine the role of ERbeta in the development of chronic heart failure after experimental myocardial infarction (MI). Female ERbeta null mice (BERKO(Chapel Hill)) and wild-type littermates (WT) were ovariectomized, given 17beta-estradiol, and subjected to chronic anterior MI (MI; BERKO n=31, WT n=30) or sham operation (sham; BERKO n=14, WT n=14). At 8 weeks after MI, both genotypes revealed left ventricular remodeling and impaired contractile function at similar average infarct size (BERKO-MI 32.9+/-5% versus WT-MI 33.0+/-4%); however, BERKO mice showed increased mortality (BERKO-MI 42% versus WT-MI 23%), increased body weight and fluid retention (P<0.01), higher ventricular pro-ANP expression (BERKO-MI 27.9-fold versus sham, WT-MI 5.2-fold versus sham; BERKO-MI versus WT-MI P<0.001), higher atrial natriuretic peptide serum levels, and increased phospholamban expression (P<0.05) compared with WT mice. Systemic deletion of ERbeta in female mice increases mortality, aggravates clinical and biochemical markers of heart failure, and contributes to impaired expression of Ca(2+)-handling proteins in chronic heart failure after MI. Further studies are required to delineate the relative importance of cardiac and vascular effects of ERbeta and the role of ERalpha in the development of heart failure.

Experimental models of heart failure

Background Most successful and reproducible animal models of chronic heart failure (HF) include: increased peripheral resistance, rapid ventricular pacing, arteriovenous shunt, supravalvular stenosis, chronic heart block, repetitive transmyocardial direct current (DC) shock. The main limitation of all these approaches was the lack of stability of the left ventricular (LV) dysfunction. Methods We have described a stable and reproducible animal model of LV dysfunction mediated by ischemic loss of contractive myocardium, which is suitable for chronically studying the complex pathophysiology of HF. This model incorporates conscious dogs with a chronic anterior myocardial infarction (MI). Once the MI is stabilized the progression of the ischemic disease is produced by injecting into the circumflex coronary artery 1–2 cc of latex microspheres to cause embolization of microcirculation. This procedure is repeated 3–5 times over several weeks and, at the end, it results in a spread ischemic damage and a significant loss of ventricular systolic function. Results The healed MI results in a depression of heart rate variability and baroreflex sensitivity in a subgroup of dogs. In these dogs the depressed vagal control of the heart is associated with elevated arrhythmic risk. On the contrary in dogs with preserved cardiac reflexes the arrhythmic risk is low. In the high risk group a profound electrophysiological remodelling occurs with the MI and progresses once LV dysfunction is created while the low risk dogs tolerate the embolization procedure with a loss in LV function but without the changes in the cardiac electrical stability. Conclusion Experimental preparations based on a chronic MI and progression of the ischemic damage toward a chronic LV dysfunction has provided important information concerning autonomic and electrophysiologic alterations associated with sudden cardiac death.

Quantitative clinical assessment of chronic anterior myocardial infarction with delayed enhancement magnetic resonance imaging and QRS scoring

Background Both the regional and global myocardial extent of chronic myocardial infarction (MI) are important prognostic factors for length and quality of life and also crucial for the choice of therapy in patients with ischemic heart disease. Our aim was to develop and validate techniques for comparison between regional and global size of remote anterior MI in the left ventricle quantified with both magnetic resonance imaging (MRI) and electrocardiogram (ECG). Methods Delayed-enhancement (DE) MRI was used as a clinical “gold standard” for MI size to evaluate the extent of MI estimated with the commonly available standard 12-lead ECG. A method for comparing global and regional quantifications of MI with DE-MRI and ECG was developed. The Selvester QRS-scoring system was used for estimating MI size electrocardiographically. Results Twenty-five patients with chronic single anterior MI, documented with DE-MRI, were studied. The best agreement for mean % MI per regional segment of the left ventricle was found in the middle third (26% vs 27%), whereas the most significant discrepancy was found in the apex (56% vs 30%). The global MI size of the left ventricle averaged 21 ± 9% with DE-MRI and 22% ± 12% with ECG, with a correlation of r = 0.40 ( P <.05). Conclusions The current Selvester QRS scoring system performs well for quantifying anterior MI in the mid-regions of the left ventricle. The diagnostic performance of the Selvester QRS-scoring system for quantifying MI in the other regions, particularly the left ventricular apex, can potentially be improved, with DE-MRI as the gold standard.

In-vivo electrophysiological study in mice with chronic anterior myocardial infarction.

An increasing number of genetically altered mice with specific molecular cardiac defects are being assessed by electrophysiological studies and ECG monitoring. This approach should allow for the identification of critical genes involved in the arrhythmogenesis in myocardial infarction. Therefore it was the aim of this study to establish a standard for the in-vivo electrophysiological characteristics in the mouse model of chronic anterior myocardial infarction. Using a minimized, invasive, in-vivo electrophysiological study, surface ECG parameters, sinus node function, atrial, atrio-ventricular and ventricular conduction and ventricular repolarization, and enhanced vulnerability to atrial and ventricular arrhythmia were studied in 20 wild-type C57BL/6 mice either under control or 11 weeks after large anterior myocardial infarction induced by ligation of the left anterior descending coronary artery. Telemetric ECG recording was performed in the same animals at baseline unrestrained, conscious condition to study surface ECG parameters, heart rate variability and the prevalence of supraventricular and ventricular arrhythmia. During electrophysiological study, infarcted mice showed an 81% increase of the angle of the QRS axis (p < 0.001) and a prolongation of the P wave by 23% (p = 0.01), the QRS complex by 39% (p = 0.001), the QT interval by 23% (p<0.05), the QT(c) interval by 30% (p < 0.005) and the JT(c) interval by 31% (p < 0.05) in comparison to control animals. Furthermore, there was a prolongation of the atrio-ventricular interval by 28% (p < 0.0005) and the atrio-ventricular functional refractory period by 26% in infarcted animals (p < 0.05), and inducibility of ventricular tachycardia in 4 of 6 infarcted versus in none of control animals (0 < 0.01). During telemetric ECG recording, there was a marked increase in ventricular ectopic activity in infarcted mice in comparison to controls (p < 0.05). Heart rate and time- and frequency-domain of heart rate variability were not significantly different in both groups (p > 0.05, respectively). The mouse model of chronic anterior myocardial infarction is associated with significant atrial and ventricular conduction disturbances and vulnerability to ventricular arrhythmia and thus may provide a highly valuable tool to study molecular determinants of arrhythmogenesis in myocardial infarction.

Echocardiographic transponder-guided catheter ablation feasibility and accuracy.

The utility of echocardiography for catheter guidance during percutaneous endocardial ablation is increasingly apparent. However, the technique is currently imperfect due to limitations in discerning the ablation electrode from other parts of the catheter shaft. To examine the feasibility and accuracy of echocardiography-guided ablation using commercial ablation catheters fitted with a transponder to improve localization of the ablation electrode. Fifteen healthy pigs and five pigs with chronic anterior myocardial infarction were studied. In healthy animals, echocardiographically distinct endocardial sites in right and left cardiac chambers were targeted for ablation. In infarcted animals, the left ventricular infarction border zone was targeted. Both intracardiac (ICE; 12.5 megahertz and 5 megahertz) and transesophageal echocardiographic (TEE) techniques were utilized. In healthy animals, transponder-guided ablation was feasible with each of the echocardiographic techniques. Accuracy was 82 % (45 of 55 lesions) with ICE-12.5 MHz, 87 % (27 of 31 lesions) with ICE-5 MHz, and 81 % (22 of 27 lesions) with TEE. In infarcted animals, the accuracy was 38 % (3 of 8 lesions) for ICE-5 MHz and 38 % (3 of 8 lesions) for TEE. Errant lesions in healthy animals were observed in earlier experiments, due to operator misinterpretation of the plane of imaging. Errant lesions in infarcted animals were observed throughout the experimental series, and may have been due to a variable relationship between echocardiographic and histologic infarction border zones. Echocardiographic transponder-guided catheter ablation is feasible. Accuracy for normal endocardial targets was excellent, less so for chronic infarction border.

Selective Class III Antiarrhythmic Properties of a Novel Agent, UK‐66,914, During Chronic Myocardial Infarction

Antiarrhythmic Properties of UK‐ 66,914. UK‐66,914 is a potent Class III antiarrhythmic agent that has no effect on conduction velocity in normal tissue in vitro. The present study was performed to evaluate the influence of UK‐66,914 on conduction velocity in vivo in canine hearts with a previous myocardial infarction. Detailed three‐dimensional mapping of the heart in vivo was obtained using simultaneous recordings from 232 transmural sites. In dogs with a chronic anterior myocardial infarction, UK‐66,914 (50 μg/kg) did not alter conduction velocity in regions exhibiting normal conduction (gt; 50 cm/sec) or regions with slowed conduction (&lt; 50 cm/sec) despite an 11%‐15% increase in the ventricular effective refractory period. UK‐66,914 prevented the induction of ventricular tachycardias by programmed electrical stimulation due to lengthening of the effective refractory period with no direct or indirect effects on conduction velocity in dogs with chronic infarcts of 1‐year duration. Because the endocardial border zone surrounding the infarct was critical to the development of the reentrant pathway in vivo, studies were performed in tissue from this region in vitro utilizing a high‐resolution, 224 bipolar grid recording array. The effects of UK‐66,914, d‐sotalol, and procainamide on conduction velocity were compared in this region at concentrations that elicited a comparable increase in the effective refractory period of 40 msec. UK‐66,914 and d‐sotalol did not alter conduction velocity in regions with conduction velocities &gt; 30 cm/sec, 15‐30 cm/sec, or &lt; 15 cm/sec, whereas procainamide significantly decreased conduction velocity at all three levels. Evaluation of the hemodynamic profile of UK‐66,914 revealed no negative ionotropic effects in conscious dogs even at doses twentyfold those required to elicit increases in the effective refractory period. Therefore, UK‐66,914 is a potent and specific Class III antiarrhythmic agent, which does not alter conduction velocity in hearts with a previous myocardial infarction and exerts no negative inotropic effects.

Surface Potential Distribution on the Human Thoracic Surface in Left Bundle Branch Block

The sequences of myocardial excitation in the cases of human LBBB have been studied by the surface mapping technique. Analysis of the surface map patterns of 12 subjects has enabled 4 different types to be described. It is suggested that Type I represents a complete LBBB in the presence of an intact right bundle branch, while Types II and III show different degrees of conduction defect in the right bundle branch, too. The left ventricular activation of these 3 types has a similar pathway in phases II and III which is determined by orientation of the main subepicardial muscle layer coursing through the apex and terminating in the anterobasal region. The terminal anterobasal activation in the cases of LBBB has not only theoretical, but clinical significance, since in the presence of anteroseptal myocardial infarction the signs of necrosis must be hidden not in the early, but in the terminal parts of the QRS complex of conventional ECG. The lack of terminal anterior positivity of surface maps in the case of LBBB may be indicative of chronic anterior myocardial infarction.

Noninvasive assessment of cardiac function and ventricular dyssynergy by precordial Q wave mapping in anterior myocardial infarction.

To determine whether multiple lead precordial electrocardiographic recordings offer an improved index for noninvasive estimation of left ventricular hemodynamic function and segmental dyssynergy, precordial mapping was performed in patients with anterior myocardial infarction, and the number of pathologic Q waves (greater than or equal to 0.04 sec) was counted (Q-Index). Left ventricular function was determined by cardiac catheterization and angiography and correlated with the Q-Index. The Q-Index correlated well with dyssynergy extent (r = 0.84) and inversely with ejection fraction (r= -0.87), stroke work index (r = -0.79) and cardiac index (r = =0.66). Three patient groups were defined by Q-Index; group I, 0.04 sec Q complexes less than 15; group II, 15-25; group III, 26-35. Q-Index related closely to functional classification and survival (mean follow-up 12.2 months): group I, 91%; group II, 81%; group III, 40%. Thus 35-lead precordial Q wave mapping with determination of total number of pathologic Q waves permits practical, atraumatic assessment of hemodynamic and functional status and allows prediction of survival in acute and chronic anterior myocardial infarction.