Acute Coronary Syndromes (ACS)

Acute Coronary Syndromes (ACS)

• An acute coronary syndrome is most commonly caused by atherosclerotic plaque rupture in 90% of cases.
• Other causes of ACS include heart valves issues, congenital abnormalities, coronary artery dissection, and coronary vasospasm.

Unstable Angina, Non-STEMI, and STEMI

• Unstable Angina involves a partially occlusive thrombus with no myocyte necrosis and no ECG changes.
• Non-STEMI involves a partially occlusive thrombus, with myocyte necrosis and ST-segment depression and/or T-wave inversion on ECG.
• STEMI involves a completely occlusive thrombus, myocyte necrosis, and ST-segment elevation, potentially with ST-segment depression and/or T-wave inversion on ECG.

Atherosclerosis-Induced Coronary Thrombosis

• Chemical factors that destabilize atherosclerotic lesions include T-lymphocytes and metalloproteinases.
• T-lymphocytes produce Interferon-y, which inhibits collagen synthesis.
• Metalloproteinases degrade the interstitial matrix.
• Turbulent blood flow, which increases in SBP and HR contractility, contributes to atherosclerosis-induced coronary thrombosis.

Pathology of Infarction (Immediate)

• Oxygen deprivation leads to aerobic to anaerobic metabolism, lactic acid accumulation, and lowered pH.
• Reduction in ATP affects the Na + K + ATPase pump and alters membrane potential.
• Arrhythmias and calcium release lead to cell death, with activation of degradation enzymes.

Pathology of Infarction (5+ Days Later)

• A necrotic myocardium clears.
• Collagen deposits resulting in scar tissue formation
• "Yellow softening" occurs as myocardial cells and connection tissue are removed.
• The infarcted zone becomes thinner and dilated, leading to ventricular wall weakness.

Functional Alterations Post-Infarction

• Impaired contractility and compliance are common functional alterations post-infarction.
• Systolic dysfunction leads to decreased cardiac output and can result in hypokinetic and akinetic conditions.
• Diastolic dysfunction impairs relaxation, increasing ventricular pressure.
• Stunned myocardium experiences systolic dysfunction that gradually recovers days later; the tissue is stunned but not necrotic.

Ischemic Preconditioning and Ventricular Remodeling

• Tissue becomes more resistant to future ischemic episodes with ischemic preconditioning.
• Infarct expansion occurs: thinning and dilation due to "slippage" between muscle fibers.
• Thinning and dilation of infarct zone increases wall stress, impairs contractile function, and increases chances of aneurysm.

Clinical Features of Acute Myocardial Infarction

• Angina is more severe, lasts longer, and radiates more widely.
• Pain continues even with rest.
• Sublingual nitroglycerin is ineffective.
• Sympathetic response with intense discomfort and baroreceptor unloading resulting from a drop in pressure is activated.
• Signs of acute myocardial infarction include diaphoresis, tachycardia, and cool, clammy skin.
• An inflammatory response occurs in response to tissue injury, involving IL-1 and TNF-a.
• Other signs include a low-grade fever.
• MI symptoms may be exceptions in diabetic patients.

Diagnosing ACS

• Common blood biomarkers used to diagnose ACS include patient's presenting symptoms, acute ECG abnormalities, and detection of serum markers of necrosis.

Treatment of ACS

• Rapid treatment aims to limit damage and complications.
• Therapy must address intracoronary thrombus and restore myocardial oxygen balance.
• All patients require continuous ECG monitoring, bed rest, supplemental oxygen (with risks involved), and analgesics.

Drug Treatments for Unstable Angina and Non-STEMI

• Anti-ischemic drugs include Beta-Blockers and Calcium Channel Blockers.
• Nitrates are also used.
• Anti-platelet drugs include ADP Receptor inhibitors and Aspirin.
• Anti-coagulants include Heparin.

Fibrinolytic Therapy vs. Percutaneous Coronary Intervention

• Emergent PCI should be available within 90 minutes (120 minutes if transferring to a PCI-capable hospital).

Major Complications of a Myocardial Infarction

• Recurrent ischemia is reduced with thrombolytic therapy and further reduced with percutaneous coronary revascularization.
• Inadequate residual coronary blood flow indicates recurrent ischemia.
• Arrhythmias result from anatomic interruption of blood flow to structures of the conduction pathway.
• SA node is supplied by the right coronary artery in 70% of patients
• AV node is supplied by the right coronary artery in 85% of patients
• Left and Right Bundle Branch relies on the Left anterior descending artery
• Heart Failure develops due to impaired contractility and myocardial stiffness.
• Cardiogenic Shock causes severely decreased cardiac output and hypotension (SBP < 90mmHg).
• Papillary Muscle Rupture mechanical complications result in mitral regurgitation and can be lethal.
• Ventricular Free Wall Rupture is infrequent but can lead to cardiac tamponade, where blood moves from the LV to pericardial fluid.
• Ventricular Septal Rupture involves blood moving from LV to RV and can cause volume overload of pulmonary capillaries.
• True Ventricular Aneurysm involves an outward bulge of the ventricular wall also termed Dyskinesis
• Dyskinesis can result in thrombus formation, ventricular arrhythmias, and Heart Failure - Reduced cardiac output
• Pericarditis causes sharp, stabbing pain similar to myocardial infarction.
• Thromboembolism happens due to thrombus formation due to stagnant blood flow.

Heart Failure

• Heart Failure occurs when the heart cannot pump blood forward at an adequate rate to meet the metabolic demands of the body.
• The prevalence of heart failure is increasing due to the aging population and interventions that prolong survival after cardiac damage.
• Systolic HF is characterized by insufficient contractility, increased end-diastolic volume, reduced ejection fraction (Normal EF = 55-70%), and increased end-systolic volume.
• Diastolic HF is characterized by reduced compliance, reduced end-diastolic volume, normal ejection fraction (Normal EF = 55-70%), and reduced end-systolic volume.

Compensatory Mechanism for Heart Failure

• Short-term mechanisms include the Frank-Starling Mechanism and Neurohormonal Activation.
• Long-term mechanisms include Ventricular Hypertrophy and Remodeling.
• The Frank-Starling Mechanism offsets heart failure through increasing chamber emptying, higher end diastolic volume, greater wall stretch, and greater force of contraction.
• Neurohormonal Activation results in SNS Activation. Increase in HR and Ventricular Contractility
• SNS Activation increases cardiac output, vasoconstriction of systemic arteries, and maintains mean arterial pressure (at the expense of skin, viscera, kidneys).
• The Renin-Angiotensin-Aldosterone System causes renin release from the kidneys.
• Renin release results in decreased salt delivery to the kidney, stimulation of B-receptors by the Sympathetic Nervous System, and formation of Angiotensin II.
• Angiotensin II is a potent vasoconstrictor, increasing intravascular volume, causing Thirst, Aldosterone section, and Reabsorbs sodium.
• The Renin-Angiotensin-Aldosterone System causes Rise in intravascular volume augments cardiac output. This system also activates Antidiuretic Hormone (Vasopressin)
• Arterial baroreceptors and Angiotensin II release mediates antidiuretic Hormone release.

Response to Heart Failure

• Ventricular Hypertrophy and Remodeling respond to increased wall stress by increased volume and pressure.
• Eccentric hypertrophy develops due to volume overload.
• Concentric hypertrophy develops due to pressure overload.
• Clinical features/manifestations of symptomatic (decompensated) HF include Dyspnea, pulmonary venous congestion, and Orthopnea.
• Clinical features/manifestations of symptomatic (decompensated) HF include Decreased cardiac output resulting in Dulled Mental and Skeletal Muscle Fatigue.
• Mental fatigue is caused by Low Cerebral Perfusion
• Muscle fatigue is caused by Low Perfusion
• Clinical features/manifestations of symptomatic (decompensated) HF include Right Side Heart Failure causing Peripheral edema and venous distension.
• Common physical signs of HF include cachexia, poor perfusion, and Pulmonary Rales.
• Cachexia May be present in obese HF patients
• Poor Perfusion May see Dusky skin, Sweating, and Rapid Breathing.
• Common treatment strategies related to Diastolic HF (HFpEF) is to Address correctable causes of impaired diastolic function, Relief of pulmonary and systemic congestion
• The treatment strategies for Diastolic HF address Hypertension, and Coronary Artery Disease
• The treatment strategies for Systolic HF with Diuretics, Venous vasodilators, and Arterial vasodilators.
• Diuretics = elimination of sodium and water resulting in Reduction in intravascular volume and venous return
• Venous vasodilators = dilation of veins which Increases capacity of veins to storage blood
• Arterial vasodilators = dilation of arteries which Reduction in afterload reducing the work of the heart and increasing stroke volume
• Positive Inotropic drugs = enhance force of ventricular contraction which Increase contractility resulting in increased stroke volume
• This prevents irregular heart rhythm (arrhythmias)
• Arrhythmia treatment is also with Anti-arrhythmic drugs (e.g. Amiodarone) = prolongs action potential and refractory period
• Implantable Cardioverter – Defibrillator (ICD) is used if LVEF < 35% because Reduces risk of cardiac death
• Heart failure also uses Surgical management techniques that are Improved quality of life and Extension of life
• Surgical management of Heart failure can result with Risks Rejection (counteracted w/ immunosuppressant therapy), and Consequences related to immunosuppression

Quiz 7 - Acute Coronary Syndromes

• Greater than 90% of all acute coronary syndromes result from atherosclerotic plaque rupture
• Metalloproteinases are chemical factors that destabilize atherosclerotic lesions.
• Turbulent blood flow does NOT stabilize atherosclerotic lesions and prevent plaque rupture.
• Transmural infarcts can be identified by significant ST-segment elevation
• A greater amount of collateral vessel blood supply to the affected region DOES NOT increase the amount of heart tissue death during a myocardial infarction
• Post-myocardial infarction (5+ days later), a period of "yellow softening" results in destruction of connective tissue and replacement with scar tissue (collagen).
• The difference in symptoms that would help identify if an individual is having an acute myocardial infarction as opposed to unstable angina is that the pain is not relieved with sublingual nitroglycerin.
• CK-MB Creatine kinase isoform is associated with heart tissue necrosis
• Beta blockers is an example of anti-ischemic drugs used in the treatment of acute coronary syndromes?
• A ventricular free wall rupture may cause cardiac tamponade resulting from a myocardial infarction.

Quiz 8 - Heart Failure

• When discussing cardiac performance, the term "compliance" is defined as The ease or difficulty to which the heart chamber can be filled
• Diastolic heart failure is characterized by a normal ejection fraction and reduced stroke volume.
• Systolic heart failure is characterized by a reduced ejection fraction and Reduced stroke volume.
• Angiotensin II formation is caused by Renin release from the kidneys
• Aldosterone secretion results in the reabsorption of Sodium while antidiuretic hormone release results in the retention of Water.
• Ventricular remodeling in systolic heart failure is due to volume overload and termed eccentric hypertrophy.
• Ventricular remodeling in diastolic heart failure is due to pressure overload and termed concentric hypertrophy.
• Decreased circulating volume (decreased preload) DOES NOT worsen symptoms in patients with chronic compensated heart failure.
• Dyspnea, or abnormal breathing, is a common symptom in heart failure patients that results from pulmonary venous congestion.
• is the most potent diuretic loop diuretics.