Acute coronary syndrome

Article written and reviewed by Dr Luca Moretti

Acute coronary syndrome is a working diagnosis made when the clinical presentation suggests recent-onset or rapidly worsening myocardial ischemia. It includes myocardial infarction with persistent ST-segment elevation, myocardial infarction without ST-segment elevation, and unstable angina. The term therefore describes the initial clinical problem and mandates an urgent pathway but does not by itself identify the mechanism, presence of necrosis, or definitive strategy.
The spectrum is first separated by the electrocardiogram. Persistent ST-segment elevation or an equivalent occlusion pattern directs immediate reperfusion without waiting for troponin results. In its absence, symptoms, serial tracings, and high-sensitivity cardiac troponin distinguish NSTEMI, unstable angina, and alternative diagnoses.

The most common form results from atherothrombosis, the sudden formation of a thrombus over an atherosclerotic plaque complicated by rupture, superficial erosion, or a calcified nodule. Nonatherothrombotic causes also exist, including spontaneous coronary artery dissection, embolism, vasospasm, microvascular dysfunction, and a severe oxygen supply-demand imbalance. Effective treatment depends on identifying the true mechanism.
Acute coronary syndrome is a time-dependent emergency. With persistent coronary occlusion, necrosis progressively extends from the subendocardium toward the epicardium, while malignant arrhythmias, heart failure, and shock may occur before biochemical confirmation. The regional network must reduce delays among symptom onset, first medical contact, electrocardiographic diagnosis, and reperfusion.

Widespread use of high-sensitivity troponin has reclassified as NSTEMI many events formerly considered unstable angina. It has also made detection of nonischemic myocardial injury common, especially in older adults, kidney failure, heart failure, and critical illness. An elevated biomarker therefore does not automatically equal infarction or justify indiscriminate antithrombotic treatment.
Epidemiological incidence depends on the population, age, surveillance system, and definition used. In countries with reperfusion networks, in-hospital STEMI mortality has fallen, while mean age, comorbidities, and the proportion of NSTEMI have increased. Residual risk remains particularly high with shock, cardiac arrest, multivessel disease, kidney failure, diabetes, frailty, or ventricular dysfunction.

Improved acute survival has shifted part of the burden toward recurrence, heart failure, and disability. Treatment therefore does not end when the culprit artery is reopened: secondary prevention must begin during hospitalization and continue with intensive lipid lowering, risk-factor control, rehabilitation, medication adherence, and structured follow-up.

Etiology, risk factors, pathogenesis, and pathophysiology

The predominant cause is plaque rupture. Disruption of the fibrous cap exposes the necrotic core and tissue factor to blood, promoting platelet adhesion, thrombin generation, and fibrin deposition. The probability of occlusion depends not only on lesion morphology but also on local flow, platelet activity, coagulation, and fibrinolytic capacity.
In superficial erosion, thrombus forms over a denuded endothelial surface without macroscopic cap rupture. Culprit plaques are often rich in matrix and smooth-muscle cells, with less lipid than ruptured plaques. Disturbed flow, neutrophils, and neutrophil extracellular traps contribute to luminal-surface injury.

A calcified nodule is a less frequent mechanism. Calcium fragments may protrude through the surface of a severely calcified plaque and trigger thrombosis, particularly in tortuous arteries of older patients, people with diabetes, or those with kidney disease. The lesion is also difficult to dilate and may require specific preparation before stenting.
Initial platelet adhesion is mediated by interactions among von Willebrand factor, collagen, and platelet receptors. Activation releases ADP and thromboxane A2, changes the glycoprotein IIb/IIIa receptor, and permits fibrinogen binding. Antiplatelet therapy interferes with different nodes of this cascade but does not eliminate the parallel contribution of coagulation.

The tissue factor pathway generates thrombin, which converts fibrinogen into fibrin and amplifies platelet activation. Parenteral anticoagulation reduces thrombus propagation during the acute phase, while mechanical reperfusion restores the lumen when occlusion persists. Antiplatelet therapy, anticoagulation, and PCI therefore have complementary rationales.
The coronary thrombus evolves through propagation and lysis. It may completely occlude the vessel, shrink spontaneously, reform, or embolize distally; this dynamic nature explains variability in symptoms and ECG findings and why angiography may show only a moderate lesion after a clinically important event.

Local vasoconstriction may aggravate a thrombotic stenosis through endothelial dysfunction, platelet mediators, and sympathetic activation. In primary vasospasm, by contrast, intense transient arterial contraction may be the main mechanism even without an obstructive plaque. A prolonged episode may cause necrosis and infarction.
Spontaneous coronary artery dissection compresses the true lumen through an intramural hematoma, with or without a visible intimal tear. It is especially important in younger women and the peripartum period and is frequently associated with systemic arteriopathies such as fibromuscular dysplasia. Its biology differs from atherothrombosis, often making conservative management preferable when flow and stability permit.

A coronary embolism may arise from atrial fibrillation, ventricular or atrial thrombi, prosthetic valves, endocarditis, cardiac tumors, paradoxical embolism, or procedures. It may obstruct an otherwise normal vessel and requires investigation of the embolic source because antiplatelet therapy alone does not necessarily correct recurrence risk.
Atherothrombotic risk increases with cumulative exposure to apoB-containing lipoproteins, smoking, hypertension, diabetes, kidney disease, and chronic inflammation. Elevated lipoprotein(a) and genetic predisposition contribute to premature risk; these factors primarily increase disease burden and the likelihood that one of many plaques becomes clinically active.

Smoking has proaggregatory, vasoconstrictive, inflammatory, and endothelial effects in addition to accelerating atherosclerosis. Even modest consumption is not free of cardiovascular risk. Cessation after an acute event rapidly reduces part of the risk and is one of the most effective prognostic measures.
Diabetes promotes diffuse atherosclerosis, endothelial dysfunction, platelet activation, and microangiopathy. Autonomic neuropathy may attenuate pain perception, and diabetes is associated with later presentation, multivessel disease, and worse prognosis. Acute glucose management must avoid both severe hyperglycemia and hypoglycemia.

Chronic kidney disease combines vascular calcification, inflammation, platelet dysfunction, anemia, and greater bleeding risk. Troponin may be chronically elevated, but a dynamic change accompanied by ischemia retains diagnostic significance. Antithrombotic doses and contrast use must be adjusted to kidney function.
Acute infections, surgery, emotional stress, and unaccustomed vigorous exercise may act as precipitants in susceptible people. Sympathetic activation, inflammation, blood-pressure changes, and a prothrombotic state may contribute to the event. In most cases, however, no single necessary or sufficient trigger can be identified.

Cocaine and amphetamines increase risk through adrenergic stimulation, tachycardia, hypertension, vasospasm, and thrombotic activation. The history should be nonjudgmental because the information changes treatment. Beta-blockers should not be absolutely excluded in every circumstance, but intoxication with vasospasm requires specific assessment.
Reduced flow causes a rapid ischemic cascade. Metabolism and diastolic relaxation change first, followed by regional contractility, electrophysiology, and finally symptoms. Troponin may initially remain normal, so a diagnostic ECG and convincing presentation must not await biochemical confirmation before reperfusion.

With persistent coronary occlusion, necrosis advances according to the wavefront model, from the more vulnerable subendocardium toward the outer layers. Its rate depends on occlusion duration, the territory at risk, collateral flow, myocardial demand, and episodes of spontaneous reperfusion. The portion that remains viable is salvageable myocardium.
The subendocardium is vulnerable because it experiences greater wall stress and systolic compression. Tachycardia shortens diastole, hypotension lowers perfusion pressure, and hypertrophy increases the diffusion distance for oxygen; these factors may amplify ischemia caused by an epicardial lesion.

Reopening the artery may be followed by reperfusion injury associated with reactive oxygen species, calcium overload, opening of the mitochondrial permeability transition pore, and inflammation. Reperfusion nevertheless remains essential: the associated injury never justifies delaying restoration of flow.
Microembolization of thrombotic and atheromatous material obstructs arterioles and capillaries. Edema, endothelial injury, intramyocardial hemorrhage, and vasoconstriction may sustain inadequate tissue perfusion despite epicardial patency; this is the substrate of no-reflow and microvascular obstruction.

In no-reflow, the treated artery may have an acceptable angiographic result while the tissue remains hypoperfused. Poor ST-segment resolution and reduced myocardial blush are clues; magnetic resonance defines its extent and consequences. The phenomenon is associated with larger infarctions and adverse remodeling.
Secondary myocardial infarction results from an acute supply-demand imbalance caused by another acute condition, without an acute coronary disorder. Anemia, hypoxemia, hypotension, shock, tachyarrhythmia, or severe hypertension may be responsible. Although it may present as suspected ACS, it requires treatment of the precipitant and individualized assessment of coronary disease.

Nonischemic myocardial injury may accompany sepsis, heart failure, pulmonary embolism, myocarditis, kidney failure, or critical stress. Troponin demonstrates cardiomyocyte injury, not its mechanism. Without evidence of ischemia, the correct diagnosis remains acute or chronic myocardial injury.
During pregnancy and the puerperium, dissection, thrombosis, and hypertensive disorders alter the prevailing etiology. Assessment must not be delayed because of radiation concerns when the mother is unstable. Cardiology, obstetrics, anesthesia, and neonatology coordinate treatment, imaging, and the timing of delivery.

Finally, the neurohormonal and inflammatory response to ischemia activates catecholamines and the renin-angiotensin-aldosterone system. It initially supports blood pressure, but persistent activation promotes ventricular remodeling, congestion, and arrhythmias. Early vessel treatment and subsequent therapy for ventricular dysfunction limit this progression.

Pathological anatomy, classification, and course

The initial clinical classification distinguishes STEMI from non-ST-elevation syndrome. It is an operational ECG-based division reflecting the need for immediate reperfusion, not a histological description of infarct depth. Early reperfusion may limit a STEMI, whereas NSTEMI may cause extensive necrosis.
The NSTE-ACS category includes NSTEMI and unstable angina. They differ by the presence of troponin-demonstrated acute ischemic myocardial injury. Because high-sensitivity assays detect small acute myocardial injuries associated with ischemia, unstable angina is now less frequent and must be diagnosed rigorously.

Anterior STEMI often results from LAD occlusion and may involve the septum, anterior wall, and apex. Proximal occlusion places a large myocardial mass at risk and increases the likelihood of shock, infranodal conduction block, apical thrombus, and wall rupture.
Inferior STEMI is more often related to the right coronary artery but may arise from the circumflex. Bradycardia, atrioventricular block, and right ventricular involvement are more frequent. Right-sided leads define right ventricular involvement and alter hemodynamic management.

Posterior infarction may present with ST depression in V1-V3, prominent R waves, and an increased R/S ratio. Leads V7-V9 may document posterior ST-segment elevation. Failure to recognize it may incorrectly classify an occlusion as ordinary NSTE-ACS.
The culprit coronary artery may appear occluded, suboccluded, irregular, or already recanalized. Angiographic severity at examination does not necessarily reconstruct the severity during pain. Endogenous thrombolysis, vasodilation, and thrombus migration may alter the appearance.

The TIMI scale describes epicardial flow from absent to normal. Achieving TIMI 3 is a procedural goal but does not automatically mean intact microvascular perfusion. Myocardial blush and ST-segment resolution add information about tissue flow.
Rupture has a disrupted cap and a cavity communicating with the lumen; erosion shows thrombus over an imaging-intact cap; a calcified nodule protrudes into the lumen. OCT provides high resolution of the surface, while IVUS penetrates more deeply and assesses plaque burden and remodeling.

In-vivo diagnosis of erosion by OCT remains indirect because the endothelium is not resolved directly. Stent-free strategies have been studied in highly selected patients but are not universal and require favorable anatomy, preserved flow, and specialist expertise.
Spontaneous dissection may show a flap with a double lumen or a long, smooth stenosis caused by intramural hematoma. Intracoronary imaging clarifies uncertain cases but may extend the dissection and should be used only when the information changes management.

MINOCA is not an etiologic conclusion. It identifies myocardial injury with clinical features of possible infarction and nonobstructive coronary arteries, meaning no stenosis of 50% or greater; MINOCA is a working diagnosis and does not require that infarction already be confirmed. Plaque, dissection, embolism, vasospasm, and microvascular disease must be distinguished from nonischemic mimics.
Myocarditis and Takotsubo syndrome may mimic ACS with pain, ECG changes, and troponin elevation. Magnetic resonance distinguishes subendocardial or transmural ischemic patterns from edema and nonischemic late enhancement. Once recognized, these conditions should not be classified as ischemic MINOCA.

Myocardial necrosis triggers a sequence of coagulation and inflammation. During the first days, neutrophils and then macrophages remove dead tissue; fibroblasts and matrix subsequently form the scar. During degradation, the wall is more fragile and susceptible to rupture.
Infarct expansion is the early thinning and dilation of the necrotic segment without new necrosis. It increases wall stress and promotes global dilation. Early reperfusion, infarct limitation, and neurohormonal therapy reduce adverse remodeling.

Stunned myocardium is viable but temporarily dysfunctional after reperfusion. Function may recover over days or weeks, so an early ejection fraction does not always represent the final value. Reassessment over time is essential before certain device decisions.
Salvaged myocardium is the portion of the territory at risk that does not progress to necrosis because of reperfusion. Its amount depends mainly on delay and the quality of epicardial and microvascular flow. It cannot be inferred from the troponin peak alone.

Microvascular obstruction appears on magnetic resonance as a hypoenhanced area within the necrosis. Intramyocardial hemorrhage identifies even more severe injury. Both predict remodeling and prognosis beyond ejection fraction alone.
The Killip classification stratifies clinical heart failure from no congestion to cardiogenic shock. Although developed before modern therapies, it retains prognostic value. It should be updated as the patient evolves because the class is not an immutable property of the event.

The SCAI shock classification organizes a dynamic continuum from at risk to extreme shock. It integrates hypotension, hypoperfusion, and response to treatment and improves communication among centers. It does not replace assessment of filling pressures, right and left ventricular function, and mechanical causes.
Postinfarction scar may be subendocardial or transmural and disrupt the electrical architecture. Channels of surviving tissue within fibrosis promote re-entry circuits and late ventricular tachycardia. Extent and location also influence function and mitral regurgitation.

Right ventricular infarction impairs left ventricular filling and may cause hypotension with venous congestion. Ventricular interdependence makes both hypovolemia and excessive fluids harmful. Recovery may be substantial if flow is restored rapidly.
Involvement of the papillary muscles may cause transient ischemic dysfunction or rupture. The posteromedial muscle is more vulnerable because it often has a single arterial supply. Rupture causes acute mitral regurgitation, pulmonary edema, and shock even with an apparently preserved ejection fraction.

Extensive septal necrosis may progress to a ventricular septal defect. The left-to-right shunt overloads the right ventricle and reduces systemic output. Anatomical size alone does not describe severity, which depends on the pressure gradient and the function of both ventricles.
Rupture of the free wall causes hemopericardium and tamponade or is contained by the pericardium and adhesions to form a pseudoaneurysm. Risk is greater after large transmural infarctions and late reperfusion. A new effusion with instability requires immediate assessment.

The final course depends on the integration of infarct size, microcirculation, ventricular function, complications, and prevention of recurrence. The simple STEMI or NSTEMI classification does not replace this assessment. Every patient should be restaged during hospitalization and follow-up.

Clinical manifestations

The history begins by precisely defining time of onset, mode of appearance, duration, location, radiation, quality, intensity, and symptom pattern. Patient-reported time does not always coincide with the start of occlusion but guides the reperfusion strategy. Intermittent episodes may indicate occlusion and recanalization.
The most typical symptom is retrosternal chest discomfort described as pressure, heaviness, squeezing, tightness, or burning. It may radiate to the arms, shoulders, neck, jaw, back, or epigastrium. An atypical description reduces probability, but no single quality excludes ACS.

Duration is often more than a few minutes, and pain may persist or recur. Failure to respond to nitrates does not confirm infarction, while relief does not exclude it. Therapeutic response must not be used as a diagnostic test.
Dyspnea may reflect ischemia as an anginal equivalent, increased filling pressures, mitral regurgitation, or pulmonary edema. It may be the principal symptom in older adults and people with diabetes. Concomitant hypoxemia also requires consideration of pulmonary embolism and respiratory disease.

Cold sweating, pallor, nausea, and vomiting result from autonomic activation and are common, especially in inferior infarction. They are not specific but strengthen suspicion when associated with compatible pain. Repeated vomiting may impair absorption of oral antiplatelet drugs.
Syncope may result from arrhythmia, atrioventricular block, severe ventricular dysfunction, a vagal reflex, or a mechanical complication. ACS with syncope requires immediate monitoring. Loss of consciousness may precede pain or prevent reliable reconstruction of timing.

Palpitations, presyncope, or cardiac arrest may constitute an arrhythmic presentation. Acute ischemia alters membrane potential, conduction, and refractoriness, creating a substrate for ventricular tachycardia and fibrillation. After resuscitation, the priority is to determine whether a treatable coronary occlusion persists.
Women, older adults, and patients with diabetes and kidney disease more frequently have nonclassic symptoms, but chest pain remains common. The concept of an atypical presentation must not become a stereotype or reduce attention to the symptoms described by the individual.

The history should seek previous coronary disease, PCI, bypass, infarction, heart failure, stroke, peripheral artery disease, and bleeding; these alter pretest probability, ECG interpretation, antithrombotic selection, and the likelihood of complex anatomy or graft occlusion.
Medication and adherence are essential: anticoagulants, antiplatelet agents, nitrates, beta-blockers, antihypertensive drugs, and lipid-lowering therapies modify risk and treatment. Recent use of PDE5 inhibitors contraindicates nitrates because of the risk of severe hypotension.

Cocaine or stimulant use, pregnancy or the puerperium, inflammatory disease, thrombophilia, atrial fibrillation, and recent infection should be elicited; these features point to alternative causes to atherothrombosis and prevent application of a standard strategy to different mechanisms.
Physical examination begins with ABC, mental status, airway patency, work of breathing, pulse, blood pressure in both arms when appropriate, oxygen saturation, and temperature. An unstable patient is treated while diagnosis proceeds, without waiting for a complete assessment.

General appearance may show agitation, pallor, sweating, or cyanosis. Peripheral perfusion is assessed through skin temperature, capillary refill, mental status, and urine output, not blood pressure alone. Hypotension without hypoperfusion and shock are not synonymous.
On cardiac auscultation, a third heart sound suggests increased filling pressures and ventricular dysfunction. A new systolic murmur raises concern for acute mitral regurgitation or a septal defect but may be faint when output is very low.

Pulmonary crackles indicate congestion, whereas relatively clear lungs with hypotension and distended jugular veins suggest right ventricular infarction. Absence of crackles does not exclude cardiogenic shock. Bedside ultrasound rapidly clarifies function and pressures.
A blood-pressure difference between limbs, an aortic-regurgitation murmur, or sudden pain radiating to the back raises suspicion of aortic dissection. Anticoagulation, antiplatelet therapy, or fibrinolysis may be catastrophic in this setting, so the alternative diagnosis must be assessed immediately.

Pleuritic pain, tachycardia, hypoxemia, and signs of venous thrombosis suggest pulmonary embolism. Right ventricular overload may elevate troponin and cause ECG changes, but echocardiographic distribution and thoracic imaging distinguish the mechanisms.
Pain reproducible on palpation favors a musculoskeletal cause but does not completely exclude ischemia. Fever, a rub, and positional pain suggest pericarditis; pneumothorax, pneumonia, esophageal rupture, and upper abdominal disease belong in the urgent differential diagnosis.

Inferior STEMI may be associated with vagal bradycardia, nausea, and hypotension. Nodal atrioventricular block may be transient, whereas infranodal block during anterior infarction suggests more extensive necrosis and a worse prognosis.
Extensive anterior STEMI may present with tachycardia, congestion, and low output. Early hypotension requires differentiation among loss of function, hypovolemia, right ventricular infarction, arrhythmia, and a mechanical complication because each requires a different intervention.

Recurrent pain after initial improvement may indicate reocclusion, spasm, stent thrombosis, or infarct extension. A new ECG should be obtained during symptoms and compared with previous tracings. The absence of change does not completely exclude ischemia.
After the initial phase, low-grade fever and leukocytosis may accompany the inflammatory response to necrosis. High or persistent fever requires investigation for infection, especially with catheters, ventilation, or shock. Endocarditis may also be the source of coronary embolism.

During the following days, new pleuritic pain with a rub may indicate early pericarditis. It must be distinguished from reinfarction, pulmonary embolism, and dissection. Troponin interpretation is difficult because it may remain elevated after the initial event.
Intense anxiety and a sense of impending death are common but neither prove nor exclude ischemia. Communication reduces the adrenergic response and improves cooperation. Psychological symptoms must not prompt premature labeling as a panic attack.

Examination must conclude with serial reassessment. Symptoms, blood pressure, rhythm, saturation, urine output, perfusion, and congestion may change rapidly. Clinical dynamics are often more informative than a single observation and must be documented alongside decision times.

Investigations and diagnosis

The first test is the 12-lead ECG, ideally obtained and interpreted within 10 minutes of first medical contact. A diagnostic STEMI tracing or occlusion equivalent activates reperfusion. Troponin must not delay transfer to the catheterization laboratory.
If the first tracing is nondiagnostic but symptoms persist, serial ECGs are required at short intervals and during recurrence. Dynamic ischemia may appear as transient ST-segment elevation, ST depression, or T-wave inversion. A single normal ECG does not exclude ACS.

V7-V9 leads are indicated when posterior infarction is suspected, especially with anterior ST depression and prominent R waves. Right-sided leads, particularly V3R and V4R, are useful in inferior infarction to document right ventricular involvement.
Patterns such as de Winter, regional hyperacute T waves, Sgarbossa criteria with bundle branch block or pacing, and diffuse ST depression with elevation in aVR may indicate severe ischemia. They must be interpreted in context and do not automatically replace urgent anatomical assessment.

Cardiac troponin I or T is the preferred biomarker. A value above the sex-specific 99th percentile defines myocardial injury, while a significant rise or fall indicates an acute component. Infarction also requires evidence of ischemia.
The ESC 0/1-hour and 0/2-hour algorithms use assay-specific initial values and absolute changes. There are no universal thresholds interchangeable among methods. The laboratory should report units, percentile, limit of detection, and validated cutoffs for the platform used.

Very early sampling may precede measurable release. If suspicion persists, serial troponin is mandatory even after a low initial value. Kidney failure, heart failure, and advanced age may increase baseline values but do not make the test unusable.
Creatinine, complete blood count, glucose, electrolytes, coagulation, and a lipid profile complete the assessment. Hemoglobin identifies anemia and bleeding risk; potassium and magnesium influence arrhythmias; kidney function guides drug doses and protection from contrast-associated injury.

A lipid profile should be obtained early because the acute phase may lower measured cholesterol. It helps establish intensive therapy and identify possible familial hypercholesterolemia. Treatment must not be delayed while awaiting results.
Echocardiography assesses regional motion, right and left ventricular function, mitral regurgitation, effusion, and mechanical complications. It is urgent in instability or diagnostic uncertainty but must not delay reperfusion when STEMI is evident.

A new regional abnormality supports ischemia but is not specific to the acute event because it may result from previous infarction, pacing, or Takotsubo syndrome. Contrast echocardiography improves visualization of the apex and detection of ventricular thrombus.
Chest radiography does not diagnose ACS but identifies edema, pneumonia, pneumothorax, or a widened mediastinum. Aortic or pulmonary CT is reserved for suspected alternative diagnoses and must not create inappropriate delays in a patient with evident coronary occlusion.

Invasive coronary angiography defines the anatomy, culprit vessel, and feasibility of revascularization. It is immediate in STEMI and in NSTE-ACS with hemodynamic instability, shock, refractory pain, dangerous arrhythmias, or persistent ischemia. Timing in other cases is risk guided.
In NSTE-ACS, the GRACE score integrates age, blood pressure, heart rate, creatinine, Killip class, cardiac arrest, ST deviation, and biomarkers. It supports prognosis and strategy but does not supersede an immediate indication created by clinical instability.

Bleeding scores, including ARC-HBR and PRECISE-DAPT in appropriate contexts, help estimate bleeding risk. They must not be used to automatically deny life-saving therapies. Ischemic and bleeding risks often share the same determinants.
OCT has sufficient resolution to show rupture, thrombus, malapposition, and dissection; IVUS assesses deeper plaque burden, dimensions, and calcium. Intracoronary imaging is recommended to guide PCI of complex lesions and clarify selected mechanisms.

In MINOCA, cardiac magnetic resonance should be performed early when possible. Patterns of edema and late enhancement distinguish infarction, myocarditis, and Takotsubo syndrome. A late examination may miss edema and reduce diagnostic yield.
Provocation testing for vasospasm and functional microvascular assessment are performed in experienced centers when the context requires. They are not part of initial STEMI stabilization but may resolve cases without an identified cause.

The differential diagnosis includes aortic dissection, pulmonary embolism, pericarditis, myocarditis, Takotsubo syndrome, heart failure, hypertensive crisis, pneumothorax, pneumonia, esophageal rupture, and abdominal causes. The priority is recognizing lethal mimics in which antithrombotic therapy may be harmful.
No single autonomous set of ACS criteria applies to all its forms. Diagnosis arises from sequential integration of the presentation, ECG, and troponin and is then reclassified according to specific STEMI, myocardial infarction, or unstable-angina criteria.

Myocardial infarction requires acute myocardial injury with at least one troponin value above the sex-specific 99th percentile and at least one item of evidence of ischemia: symptoms; new or presumed new ischemic ECG changes; pathological Q waves; imaging evidence of an acute coronary disorder; or new or presumed new loss of viable myocardium or a regional abnormality with an ischemic pattern.
A diagnosis of unstable angina requires acute ischemia without detectable acute myocardial injury at the time of assessment and after reasonable exclusion of alternatives. Nonspecific pain with negative troponins is insufficient. CCTA or functional testing may be appropriate in selected low-risk patients.

Cardiac arrest with persistent ST-segment elevation indicates urgent angiography when consistent with goals of care. Without ST elevation, immediate angiography is not automatic for everyone and depends on instability, persistent ischemia, and the probability of a coronary cause.
Time documentation should record onset, the call, first contact, ECG, diagnosis, medication, arrival at the center, and guidewire passage; these intervals identify modifiable delays and are part of network quality, not merely administrative data.

Before discharge, ejection fraction, residual anatomy, etiologic diagnosis, complications, and the antithrombotic plan should be documented. A generic final diagnosis of unspecified ACS is inadequate when the data permit more precise classification.

Treatment and prognosis

Management begins with network activation, monitoring, intravenous access, an available defibrillator, and simultaneous treatment of instability. A diagnostic prehospital ECG permits direct transport to a PCI-capable center, reducing avoidable transfers and delays.
Oxygen is indicated in hypoxemia, particularly when saturation is below 90%, and is not routinely recommended in normoxemic patients. Hyperoxia has shown no benefit in uncomplicated infarction and may cause vasoconstriction. Saturation should guide administration.

Nitrates relieve pain and congestion by reducing preload and coronary tone but do not directly improve survival. They are contraindicated in hypotension, suspected right ventricular infarction with critical preload, and recent PDE5-inhibitor use. Response does not confirm the diagnosis.
Morphine is reserved for severe persistent uncontrolled pain because it may slow absorption of oral antiplatelet drugs and cause hypotension or respiratory depression. Its use must not become automatic or delay reperfusion.

Aspirin is administered rapidly in the absence of contraindications, with a chewable loading dose followed by maintenance. Irreversible inhibition of platelet cyclooxygenase reduces thromboxane A2 and propagation of the platelet aggregate.
A P2Y12 inhibitor completes dual antiplatelet therapy. Ticagrelor or prasugrel is preferred to clopidogrel in appropriate patients with ACS undergoing PCI; prasugrel is contraindicated after stroke or TIA. Age, weight, bleeding, anticoagulation, and invasive strategy guide selection.

Indiscriminate pretreatment with a P2Y12 inhibitor before the anatomy is known is not recommended in NSTE-ACS when early angiography is planned. If the wait exceeds 24 hours, clopidogrel or ticagrelor may be considered in selected patients. The risk of delaying CABG must be assessed.
Parenteral anticoagulation is chosen according to strategy and kidney function. Unfractionated heparin, enoxaparin, and bivalirudin have specific roles; fondaparinux in NSTE-ACS requires additional heparin during PCI to prevent catheter thrombosis.

In STEMI, primary PCI is preferred when it can be performed within recommended times. If the expected delay exceeds 120 minutes from diagnosis and onset was within 12 hours, fibrinolysis is indicated in the absence of contraindications, followed by immediate transfer.
Rescue PCI is required after failed fibrinolysis, indicated by persistent pain, instability, or insufficient ST-segment resolution. Even after apparently successful lysis, a pharmacoinvasive strategy requires angiography in the following hours, not simple observation at the peripheral center.

In NSTE-ACS with shock, refractory ischemia, dangerous arrhythmias, or acute heart failure, an immediate invasive strategy is indicated. In intermediate- or high-risk patients, an invasive approach during hospitalization reduces events; precise timing integrates GRACE, ECG dynamics, and the clinical situation.
Radial access is preferred for PCI in ACS because it reduces bleeding, vascular complications, and mortality compared with femoral access. Femoral access remains necessary for some anatomies or mechanical support and requires ultrasound-guided technique and meticulous hemostasis.

Intravascular imaging is recommended to guide PCI of complex lesions. It permits sizing, calcium assessment, evaluation of stent expansion and apposition, and detection of edge dissections. Procedural quality reduces thrombosis and restenosis.
Routine thrombus aspiration is not recommended in STEMI because large trials showed no overall clinical benefit and raised a stroke signal. It may be considered as bail-out treatment for selected thrombus but must not become systematic practice.

Complete revascularization of significant nonculprit stenoses is recommended in stable patients with multivessel disease, either during the index procedure or staged according to anatomy and condition. In cardiogenic shock, initial PCI should instead focus on the culprit vessel.
In cardiogenic shock, urgent revascularization of the culprit vessel is fundamental. Vasopressors, inotropes, ventilation, and circulatory support are tailored to phenotype. A microaxial flow pump may be reasonable in selected patients, balancing benefit against bleeding, limb ischemia, and kidney injury.

The default strategy after ACS is DAPT for 12 months when bleeding risk is not high. Shorter durations, transition to P2Y12 monotherapy, or de-escalation are possible in selected patients. The decision integrates ischemic risk, bleeding, PCI complexity, and adherence.
When chronic oral anticoagulation is required, triple therapy is kept as short as possible and aspirin is generally stopped after an initial phase, with continuation of the anticoagulant and clopidogrel. The anticoagulation indication and risks of thrombosis and bleeding determine duration and composition.

A high-intensity statin should be started early. The 2026 ACC/AHA guidelines recommend an LDL-C goal below 55 mg/dL in patients with very-high-risk ASCVD and addition of nonstatin therapies to the maximally tolerated statin when needed to reach it.
The lipid profile is rechecked four to eight weeks after starting or changing therapy. Early review identifies nonadherence, insufficient response, or a need for combination therapy. The 2026 US guidelines recommend LDL below 55 mg/dL and non-HDL cholesterol below 85 mg/dL for very-high-risk ASCVD, substantially converging with the European LDL target.

Beta-blockers, ACE inhibitors, ARBs, mineralocorticoid antagonists, and heart-failure drugs are prescribed according to ventricular function, congestion, blood pressure, diabetes, and comorbidities. Not every class must be used automatically in every patient with preserved function.
Cardiac rehabilitation should be offered before discharge. Supervised exercise, education, nutrition, smoking cessation, psychological support, and risk-factor management reduce readmissions and improve functional capacity and quality of life.

Before discharge, clear medication reconciliation is required: the indication for each drug, DAPT duration, possible interactions, management of a missed dose, and warning signs of bleeding. Unsupervised interruption of antiplatelet therapy after stenting may cause fatal thrombosis.
Early prognosis is dominated by shock, cardiac arrest, infarct extent, age, kidney function, and Killip class. In the long term, ventricular function, multivessel disease, diabetes, bleeding, ischemic recurrence, adherence, and attainment of lipid goals are decisive.

Follow-up assesses symptoms, blood pressure, lipids, ventricular function, and return to activity. In patients with reduced ejection fraction, treatment is optimized and function reassessed after an appropriate interval before deciding on a primary-prevention defibrillator, unless immediate secondary-prevention indications exist.
Recovery also encompasses depression, anxiety, sleep, sexuality, driving, and work. Functional prognosis improves when these issues are addressed explicitly. Gradual return should be based on event extent, revascularization, function, and applicable regulations.

Complications

The most feared immediate complication is ventricular fibrillation, caused by electrical heterogeneity of the ischemic myocardium. It may occur before hospital arrival and is a major cause of sudden death. Early defibrillation and emergency networks determine survival.
Ventricular tachycardia may be polymorphic during active ischemia or monomorphic over scar. Arrhythmias within 48 hours have different implications from late arrhythmias unrelated to recurrent ischemia. Electrolytes, reperfusion, and ventricular function must be corrected and reassessed.

Bradycardia and atrioventricular block are common in inferior infarction and often transient. Infranodal block during anterior infarction indicates more extensive injury. Temporary pacing is reserved for symptomatic bradycardia or high-risk conduction disturbances.
Acute heart failure results from loss of contractile myocardium, persistent ischemia, mitral regurgitation, or arrhythmia. Increased filling pressures cause dyspnea and pulmonary edema. Echocardiography and treatment response distinguish the dominant mechanisms.

Cardiogenic shock combines inadequate output and systemic hypoperfusion and still has high mortality. It is not defined by blood pressure alone. Lactate, urine output, mental status, ventricular function, and mechanical causes guide reperfusion and support.
Rupture of the free wall causes hemopericardium and tamponade, often with sudden collapse. A subacute form may present with intermittent instability and effusion. Pericardiocentesis may serve as a bridge, while definitive treatment is surgical.

A postinfarction septal defect produces an acute left-to-right shunt, right ventricular overload, and low output. A new murmur and hemodynamic deterioration require urgent Doppler assessment. Surgical or percutaneous correction is planned by an expert team.
Rupture of the papillary muscle, especially the posteromedial muscle, causes acute mitral regurgitation, pulmonary edema, and shock. The left ventricle may be nondilated and apparently hyperdynamic. Transesophageal echocardiography clarifies the lesion when transthoracic imaging is inadequate.

Right ventricular infarction may cause hypotension, venous congestion, and reduced left ventricular filling. Preload must be optimized carefully: excessive fluids worsen right ventricular dilation and ventricular interdependence. Reperfusion and rhythm control are essential.
No-reflow and microvascular obstruction limit the benefit of epicardial reopening. They are associated with a large thrombus burden, delay, diabetes, and extensive infarction. No single treatment is universally effective; preventing delay and using meticulous PCI technique remain central.

Left ventricular thrombus occurs mainly after anterior infarction with apical akinesia and may embolize. Contrast echocardiography and CMR improve detection. Anticoagulation, duration, and follow-up imaging must be balanced against antiplatelet therapy.
Early pericarditis results from inflammation overlying transmural necrosis and causes pleuritic pain and a rub. Dressler syndrome is a later immune-mediated form. Both must be distinguished from recurrent ischemia and contained rupture.

A true ventricular aneurysm consists of a thinned scarred wall and may cause heart failure, arrhythmia, and thrombus. A pseudoaneurysm is a contained rupture without a normal myocardial wall and has a greater risk of rupture.
Adverse remodeling dilates the ventricle, increases wall stress, and promotes functional mitral regurgitation and chronic heart failure. Large infarction, microvascular obstruction, and late reperfusion are major determinants. Neurohormonal therapy and prevention of recurrence limit progression.

Recurrent ischemia may result from an untreated culprit lesion, residual stenoses, spasm, or new destabilization. It requires new ECGs, troponin, and anatomical assessment. It must not automatically be attributed to postprocedural musculoskeletal pain.
Reinfarction while troponin remains elevated requires a new significant biomarker rise together with clinical evidence of ischemia. Isolated interpretation of a single value is inadequate. ECG, symptoms, and coronary angiography may be decisive.

Stent thrombosis often causes a new severe infarction. Interruption of antiplatelet agents, underexpansion, malapposition, edge dissection, and high thrombogenicity are important factors. IVUS or OCT identifies the mechanism and guides correction.
Major bleeding is an independent prognostic complication and may require modification of antithrombotic therapy. Radial access, correct doses, gastric protection in at-risk patients, and minimal-duration triple therapy reduce incidence without abandoning ischemic protection.

Anemia may result from bleeding or pre-existing disease and worsen the oxygen imbalance. Transfusion does not follow one rigid threshold for everyone; the 2025 US guidelines state that maintaining hemoglobin around 10 g/dL may be reasonable in selected ACS without active bleeding.
Acute kidney injury may result from shock, congestion, contrast, and drugs. It worsens prognosis and limits therapy. Hemodynamic optimization, prudent contrast volume, and dose adjustment are more important than unvalidated drug strategies.

Ischemic stroke, systemic embolism, and intracranial hemorrhage are uncommon but devastating complications. Stroke may result from atrial fibrillation, ventricular thrombus, procedures, or fibrinolytic therapy. New neurological deficits immediately change antithrombotic treatment and imaging.
Infection, delirium, and deconditioning particularly affect older and critically ill patients. Delirium increases the risks of falls, poor adherence, and prolonged hospitalization. Safe early mobilization and removal of unnecessary devices are part of quality care.

Depression, anxiety, and post-traumatic stress may follow cardiac arrest or intensive care. Mental health influences rehabilitation, adherence, and quality of life. Screening and treatment are not ancillary to cardiovascular prognosis.
Progression of nonculprit atherosclerosis exposes patients to recurrent events even after technically successful PCI. Persistently high LDL, smoking, hypertension, and diabetes sustain risk. Systemic therapy is therefore indispensable in addition to focal lesion treatment.

The terminal consequence may be ischemic cardiomyopathy with heart failure, arrhythmias, and sudden death. Prevention depends on early reperfusion, appropriate revascularization, treatment of ventricular dysfunction, and intensive, permanent secondary prevention.