Cardiovascular Disease Pathophysiology

• The topic is the pathophysiology of cardiovascular disease.

Arteriosclerosis

• Chronic disease of the arterial system
• Characterized by abnormal thickening and hardening of vessel walls
• Results in a decreased ability of the artery to change lumen size, gradually narrowing it
• Pathophysiologic conditions include high blood pressure, insufficient perfusion of tissues, and weakening of arterial walls

Atherosclerosis

• A form of arteriosclerosis
• Thickening and hardening of vessel walls
• Caused by soft deposits of intra-arterial fat and fibrin that harden over time
• It is a leading contributor to coronary artery and cerebrovascular disease.
• It is an inflammatory disease that begins with injury to the endothelial cells that line arterial walls.

Injury Hypothesis

• Explains how injury to the coronary artery endothelium (artery lining) occurs
• Endothelial Injury: The inner lining of arteries gets damaged by factors like high blood pressure, smoking, inflammation, and high LDL cholesterol.
• LDL Accumulation & Oxidation: Damaged endothelium allows LDL to enter the artery walls, where it oxidizes and triggers inflammation.
• Immune Response: White blood cells (monocytes) attach to the damaged area, adhere to the endothelial cells through the interaction of adhesion molecules, enter the arterial wall and transform into macrophages, which worsen plaque formation
• Foam Cell Formation: Macrophages engulf oxidized LDL, turning into foam cells, and their buildup creates fatty streaks, the earliest sign of atherosclerosis
• Smooth Muscle Cell Migration: Growth factors trigger smooth muscle cells to move into the artery wall and produce matrix proteins, helping stabilize the plaque.
• Plaque Progression & Complications: Over time, the plaque grows. If its fibrous cap ruptures, a blood clot (thrombosis) may form, leading to heart attacks or strokes.
• A plaque is hemodynamically significant if it covers 60%-70% of the diameter of the coronary artery lumen, potentially causing symptoms.
• Reversal of the atherosclerotic process can occur in patients with a Total-C level of less than 150 mg/dl and HDL-C higher than 45-55 mg/dl.

Coronary Artery Disease

• One of the most common and serious effects of aging.
• Fatty deposits build up in blood vessel walls and narrow the passageway for blood movement.
• Atherosclerosis often leads to the eventual blockage of the coronary arteries and may cause a heart attack.
• Uncontrollable risk factors= sex, heredity, race, age
• Controllable risk factors include high blood pressure, high blood cholesterol, smoking, physical activity, obesity, diabetes, stress, and anger

Ischemic Heart Disease

• A result of CAD (atherosclerosis)
• Imbalance between supply and demand of the heart.
• Narrowing and hardening of the arteries leads to an imbalance between the supply and demand of blood for cardiac muscle = (Ischemia).
• Ischemia is detected by a symptom such as chest pain( angina) or indirectly by electrocardiogram

Angina

• Intermittent chest pain caused by transient, reversible myocardium ischemia
• Can results from spasm/obstruction of coronary arteries
• Reduced O2 supply to myocardium
• Characterized by myocardial ischemia and chest pain---Angina pectoris

Types of Angina

• Stable angina
• Unstable angina
• Prinzmetal's angina/Variant Angina
• Stable angina, also called “Effort Angina”, discomfort is precipitated by activity
• Stable angina has minimal or no symptoms at rest, symptoms disappear after rest/cessation of activity, and are relieved by Nitrates
• Unstable angina, aka "Crescendo angina", results in a high frequency of myocardial infarction(MI) if not treated
• Unstable angina occurs at rest, presents with severe and acute onset, and the Crescendo pain- pain increases every time.
• Prinzmetal's angina is a variant form of angina with normal coronary vessels or minimal atherosclerosis caused by a spasm of the coronary artery, and occurs at rest

Diagnostic tests for CHD, CAD, and Angina:

• Electrocardiogram (ECG)
• Exercise stress test
• Echocardiogram
• Nuclear scan

Treatments for CAD and Angina

• Aspirin: A daily dose makes the blood less likely to form clots in the coronary arteries.
• Statins: Help lower cholesterol levels.
• Beta-blockers: Block sympathetic input to decrease heart rate and oxygen demand
• ACE inhibitors: Lower blood pressure, often used in people with heart failure or after a heart attack.
• Nitrates: dilate peripheral blood vessels, decrease oxygen demand, increase oxygen supply, and relieve coronary spasm
• Digitalis: Increases the force of contraction
• Calcium channel blockers
• Antiplatelet agents

Myocardial Infarction

• Necrosis of cardiac myocytes that is irreversible and can lead to structural/functional changes
• Commonly affects the left ventricle
• Follows after more than 20 minutes of ischemia
• Structural, Functional Changes include decreased contractility, decreased LV compliance, decreased stroke volume, dysrhythmia irregular heart rate, severe inflammatory response/necrosis response, scarring results in disfuntion and can't contract like healthy cells
• Clinical manifestations include Sudden, severe chest pain that's similar to pain with ischemia, but stronger, not relieved by nitrates, radiates to neck, jaw, shoulder, left arm, indigestion nausea, and vomiting and feelings of impending doom as well as abnormal heart sounds
• Blood tests will show several markers= leukocytosis and increased blood sugar/plasma enzymes
• ECG Changes include Pronounced, persisting Q waves, ST elevation and T wave inversion
• Diagnosis represents a spectrum of acute ischemic heart diseases ranging from unstable ischemia to acute MI and is classified based on ECG and cardiac enzymes.
• Treatment- First 24 hours crucial requires Hospitalization and bed rest, ECG monitoring for arrhythmias, Pain relief with morphine/nitroglycerin, Thrombolytics to break down clots, administer oxygen and coronary artery by-pass grafts or revascularization interventions

Heart Failure

• A complex clinical syndrome where the heart is incapable of maintaining adequate cardiac output to accommodate metabolic requirements and venous return.
• Symptoms from RV (right ventricular) impairment= leg swelling, abdominal bloating & pain, weight gain and loss of appetite
• Symptoms from LV (left ventricular) impairment= shortness of breath, and shortness of breath when lying down
• Symptoms from reduced pump function= Fatigue,weakness, inability to concentrate, loss of appetite, weight loss, feels cold and Shortness of breath
• It can result from heart attack, high blood pressure/cholesterol, damage to heart valves, infection, obesity, advancing age, drug toxicity (alcohol), smoking or idiopathic causes
• In HF the heart compensates to cope with and hide the effects of heart failure through Enlargement (dilation) and Thickening of muscle fibers (hypertrophy)

Neurohormonal Responses to Help compensate for HF

• Renin-Angiotensin-Aldosterone- decreased cardiac output in HF results in decreased renal blood flow and Activates the release of renin, which converts to angiotensin I, and then angiotensin II, which is a direct vasoconstrictor.
• Adrenergic System- Decreased cardiac output causes increased sympathetic activity and increased catecholamines, resulting in vasoconstriction
• Tachycardia, this initial compensatory response eventually becomes detrimental, as it increases myocardial oxygen demand and shortens the time for coronary perfusion.
• Heart Failure Classifications- I. Normal daily activity does not initiate symptoms, II. Normal daily activities initiate onset of symptoms, but symptoms subside, III. Minimal activity initiates symptoms; patients are usually symptom free at rest, IV. Any type of activity initiates symptoms and symptoms are present at rest.

Types of Heart Failure

• Right Heart Failure=Ineffective right ventricular contractile function, Pure failure of the right side of the heart can occur acutely (as in pulmonary embolus or a right ventricular infarction).
• Left Heart Failure=Disturbance of the contractile function of the left ventricle that is Most frequently caused by left ventricular infarction, hypertension, and aortic/mitral valve disease.
• Forward Failure-Inadequate delivery of blood into the arterial system that Occurs when systemic vascular resistance is increased, producing decreased blood flow out of the ventricles that results in reduced cardiac output and hypoperfusion of vital organs and Most often occurs with aortic stenosis or systemic hypertension.
• Backward Failure-Failure of the ventricle to empty and is Usually a result of left ventricular systolic dysfunction caused by infarction or cardiomyopathy.
• Systolic Dysfunction-More familiar classic type of heart failure that is due to the heart's depressed contractility, a reduction in the force of contraction occurs and Ejection Fraction usually drops below 40%
• Diastolic Dysfunction-Slowed or incomplete ventricular relaxation and means the The heart cannot properly fill with blood because the muscle has become stiff,losing its ability to relax.
• Symptoms of systolic dysfunction include= dyspnea,fatigue, edema, persistent coughing and raspy breathing/wheezing
• Treatment for HF with Systolic Dysfunction = ACE Inhibitors, Digitalis and Diuretics

Treatments for HF:

• ACE Inhibitors- prevent the production of a chemical that causes blood vessels to narrow and so nnhibits the conversion of angiotensin I to angiotensin II.
• Digitalis- Increases the force of the heart's contractions and Also slows certain fast heart rhythms.
• Diuretics- Help the body to rid itself of extra fluid and sodium and are Commonly prescribed to reduce high blood pressure.
• Beta Blockers- Reduce the heart's workload and Work on the body's sympathetic nervous system which pours hormones like adrenaline into the bloodstream in response to stress.
• Nitrates- Used mostly for chest pain, but may also help diminish heart failure symptoms that Relax smooth muscle and widen blood vessels.

Cardiac Hypertrophy and dilatation

• The heart may undergo compensatory enlargement in the form of •Hypertrophy, Dilatation or Both

Other Cardiovascular Disease Concepts

• Compensatory hypertrophy= increase in the size and weight of myocardium and Results usually from increased pressure load and may be caused by systemic hypertension, Aortic stenosis and Mitral insufficiency, right v hypertrophy is caused by lung diease or pulmonary or tricuspid stenosis
• Compensatory dilatation- stress leads to accumulation of excessive volume of blood in the heart that causes increase in the length of the myocardial fibers and hence cardiac dilatation and can be caused by valvular insufficiency , left to tight shunts, system hypertension and cardiomypapthy/myocarditis
• Congenital heart disease (CHD) is problem with heart structure or function that is present at birth and is caused by Multifactorial inheritance (genetic/environment factors), Rubella infection, drugs or alcohol during pregnancy
• Acyanotic - Left to right shunt/ VSD/Ventricular septal defect is most common, smaller defects often close spontaneously but can cause significant right and/or left heart hypertrophy with valve changes
• Cyanotic group- Right Toleff shunt meaning entry of poorly oxygenated blood results in early cyanosis and most common example is Tetralogy of Fallot