Pathophysiology
Summary
Myocardial infarction (MI) typically presents with intense substernal chest pain that may radiate to the left arm or jaw, as well as diaphoresis, anxiety, and dyspnea. Symptoms generally persist for > 30 minutes and are not relieved by rest or nitroglycerin. An MI may present with an S4 heart sound due to the ischemic heart tissue becoming stiff and noncompliant.
Heart attacks most commonly result from left anterior descending artery (LAD) occlusion, which affects the anterior wall of the left ventricle, anterior ⅔ of the interventricular septum, and the apex. Consequently, MI with LAD occlusion can present with severe complications such as left-sided heart failure due to decreased ventricular systolic function, resulting from myocardial ischemia. Patients might also exhibit flash pulmonary edema, evidenced by bibasilar crackles on auscultation and dyspnea. The risk of ventricular ischemia also increases, leading to conduction abnormalities and potentially fatal ventricular arrhythmias like ventricular tachycardia and ventricular fibrillation, which can cause sudden cardiac death. In severe cases, cardiogenic shock might also ensue.
Conversely, occlusion of the right coronary artery (RCA) affects the SA & AV nodes, the posterior ⅓of the interventricular septum, and the posterior left ventricle. As a result, MI with RCA occlusion can lead to complications such as bradyarrhythmias, bradycardia due to SA node dysfunction, and heart block resulting from AV node dysfunction. Furthermore, ischemia due to RCA occlusion can precipitate right-sided heart failure, evidenced by signs like jugular venous distension (JVD). Severe RCA-related MI can also lead to cardiogenic shock. On ECG, MI with RCA occlusion can manifest as ST elevations on the inferior leads, specifically II, III, and aVF.
Histopathologically, the time course post-MI is crucial. Within 0-4 hours, minimal histological changes are seen. From 4-12 hours, ‘wavy fibers’ may appear, a result of non-contractile muscle fibers being pulled by adjacent contractile fibers. Also, punctate hemorrhages and early signs of coagulation necrosis are evident during this period. By 12-24 hours, frank coagulation necrosis is evident, characterized by pale cardiomyocytes, loss of nuclei, and a preserved structural outline. Contraction bands are also evident in this period, resulting from the return of blood flow leading to abnormally high intracellular Ca2+ and hypercontraction of dead cardiomyocytes. Neutrophils also begin to infiltrate the infarcted area.
From 1-3 days post-MI, the area demonstrates extensive coagulation necrosis with a pronounced neutrophilic infiltrate between the pale cells. This period is also associated with early onset peri-infarct pericarditis, localized only over the infarct area. Clinically, this pericarditis presents as pleuritic chest pain that is exacerbated on inspiration and relieved when leaning forward. Pericardial friction rub can also be observed on physical exam during this phase.
The interval of 3-14 days post-MI is characterized by a robust macrophage response infiltrating the necrotic zone. Granulation tissue becomes evident, accompanied by neovascularization. However, complications become increasingly imminent at this stage as ischemia and necrosis can results in the rupture of papillary muscles and chorda tendinae, leading to mitral regurgitation, which manifests as a holosystolic blowing murmur radiating to the left axilla, coupled with pulmonary edema & exacerbated dyspnea. Interventricular septum rupture following occlusions of the LAD and ventricular free wall from occlusion in left coronary or its branches are severe complications of this stage. Ventricular free wall rupture from LCA occlusion leads to massive hemopericardium and cardiac tamponade.
After after 14 days post-MI, fibroblasts, activated by macrophages, start depositing collagen leading to fibrotic tissue formation and the consequent scar formation. This scar reduces the risk of rupture but can introduce conduction abnormalities, potentially resulting in fatal ventricular arrhythmias and sudden cardiac death. In the long-term, weeks to months post-MI, this myocardial scar formation can impair contractile function, culminating in heart failure.
Fibroblasts eventually form scars, reducing the risk of rupture but causing long-term issues such as heart failure and ventricular wall aneurysms, which can result in systolic heart failure and ischemic strokes due to mural thrombus formation. Dressler's syndrome may also develop in the weeks to months following MI, an autoimmune pericarditis characterized by pleuritic chest pain, a pericardial friction rub, and fever with leukocytosis.
Lesson Outline
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FAQs
The hallmark symptoms of myocardial infarction (MI) often involve severe substernal chest pain or pressure that may radiate to the left arm or jaw. Accompanying these are diaphoresis, anxiety, and dyspnea. Unlike symptoms seen in stable angina, those associated with MI generally persist for more than 30 minutes and are not alleviated by either rest or nitroglycerin administration.
Myocardial infarction involving occlusion of the left anterior descending (LAD) can precipitate left-sided heart failure, leading to impaired ventricular systolic function. Manifestations of this condition include dyspnea, flash pulmonary edema, and bibasilar crackles on auscultation. Additionally, an S4 heart sound can be elicited, indicative of reduced ventricular compliance. In extreme cases, LAD occlusion can culminate in cardiogenic shock, a life-threatening emergency.
A myocardial infarction involving the right coronary artery (RCA) has distinct implications compared to one affecting the left anterior descending (LAD) artery. The RCA is responsible for perfusing the right ventricle, the posterior third of the interventricular septum, and the posterior segment of the left ventricle. An RCA occlusion can result in right-sided heart failure, commonly manifesting as jugular venous distention (JVD), and has the potential to escalate into cardiogenic shock. Additionally, because the RCA supplies the sinoatrial (SA) and atrioventricular (AV) nodes, its occlusion can precipitate bradyarrhythmia or heart block.
In the immediate hours following an MI (0-4 hours), there are typically few histological changes seen. From 4-12 hours post-MI, "wavy fibers" can be observed due to non-contractile muscle fibers being pulled by adjacent contractile fibers. Additionally, early signs of coagulation necrosis and punctate hemorrhages can be seen. By 12-24 hours, frank coagulation necrosis—presenting as pale cardiomyocytes with loss of nuclei, and preserved structural outline—becomes visible. Contraction bands may be seen due to the return of blood flow causing hypercontraction of dead cardiomyocytes. Neutrophils start appearing in the area of the infarct around this time, increasing in abundance over the next 1-3 days.
Several complications can manifest weeks to months after a myocardial infarction, largely due to the formation of fibrotic tissue in the affected myocardium. Fibrosis can precipitate ventricular arrhythmias and contribute to heart failure by impairing contractile function. Another possible complication is Dressler's syndrome, an autoimmune pericarditis triggered by IgG autoantibodies targeting myocardial antigens exposed during the acute MI phase. This syndrome presents with symptoms such as chest pain, pericardial friction rub, fever, and leukocytosis. Additionally, ventricular wall aneurysms may develop as a result of scar tissue thinning, which can lead to systolic heart failure. Embolization from mural thrombi can also occur, potentially causing ischemic stroke.
