Heart Failure Pathophysiology PDF

Pathophysiology of HF  *The goal is for the heart to maintain appropriate cardiac output Normal Cardiac Function Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013.  Normal Cardiac Functio...

Pathophysiology of HF  *The goal is for the heart to maintain appropriate cardiac output Normal Cardiac Function Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013.  Normal Cardiac Function Cardiac output (CO) is defined as the volume of blood ejected per unit time (L/min) and is the product of heart rate (HR) and stroke volume (SV) Increasing/decreasing HR and/or SV will increase/decrease CO CO=HR×SV Average heart rate = 70 beats per min x Average stroke volume = 70 ml per beat CO = 4900 ml per min Normal Cardiac Function Stroke volume is the amount of blood pumped out of the heart with each beat Stroke volume is calculated by subtracting the end systolic volume (ESV) from the end diastolic volume (EDV) CO=HR×SV SV=EDV – ESV  *The goal is for the heart to maintain appropriate cardiac output Normal Cardiac Function Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013. Factors that Affect Heart Rate The autonomic nervous system plays a key role in regulating heart rate Parasympathetic nervous system the vagus nerve innervates the SA and AV node and causes release of acetylcholine and decreases in heart rate (negative chronotropy ) Sympathetic nervous system Epinephrine and norepinephrine binds mainly to B1 receptors in heart causing increases in heart rate (positive chronotropy ), enhancing contractility (positive inotrope ), and accelerating conduction through the AV node Epinephrine travels through blood stream and is part of “the fight or flight” response and has broad systemic effects at all sympathetic receptors NE is locally released at the sympathetic nerve endings at the heart https://courses.lumenlearning.com/suny-dutchess-ap1/chapter/cardiac-physiology/  Sympathetic Nervous System Sympathetic Nervous Presynaptic receptors System + Alpha-2 – inhibit NE release + Beta-2 – facilitate release Post-synaptic receptors + Alpha-1 – vasoconstriction + Beta-1 – increase HR and contractility + Beta-2 – vasodilation, bronchodilation Beta-3 receptors are found in less concentrations in the B3 heart + negative inotrope effects  Thyroid hormones Other Hormones Thyroxine (T4) and triiodothyronine (T3) are hormones Affecting Heart produced by the thyroid gland. They enhance the Rate heart's responsiveness to catecholamines (like epinephrine and NE) Glucocorticoids Produced by the adrenal cortex, cortisol can increase heart rate indirectly by increasing the sensitivity of the cardiovascular system to catecholamines. During stress, elevated cortisol levels can lead to an increased heart rate. Non-hormonal stimulants Nicotine specifically stimulates the SNS Caffeine primarily works by blocking adenosine receptors (especially A1 and A2A receptors) in the brain and heart. Adenosine normally has a calming effect on the central nervous system, promoting vasodilation and slowing heart rate.  *The goal is for the heart to maintain appropriate cardiac output Normal Cardiac Function Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013.  Stroke volume is determined by 3 main factors: 1. Preload: the degree of stretch of the cardiac muscle fibers at the end of diastole (when the heart is filled with blood) 2. Contractility: the force with Stroke Volume which the heart muscle contracts, independent of preload 3. Afterload: the resistance of the heart must overcome to eject blood during systole  The ability of the heart to alter the force of contraction depends on changes in preload Frank Starling Law The Frank-Starling law of the heart states that the stroke volume of the heart increases in response to an increase in the volume of blood filling the heart (end- diastolic volume or EDV) when all other factors remain constant Increasing stretch of the cardiac muscle fibers enhances its contractile force up to an optimal point Low EDV à Sarcomere stretching à Myosin heads bind to actin à weak contraction during systole à SV Too much sarcomere stretching prevents optimal overlap between actin and myosin à weak contraction during systole à SV RAAS IMAGE CREDIT: DESIGNUA / SHUTTERSTOCK Natriuretic Peptides Adapted from Langenickel TH, Dole WP. Drug Discovery Today 2012;9:131–9. Copyright © 2013 Published by Elsevier Ltd  Afterload Complex physiologic concept that can be viewed as the sum of forces preventing the active forward ejection of blood by the ventricle In LVEF dysfunction, inverse relationship between afterload and stroke volume Afterload is estimated clinically by systemic vascular resistance à vasodilation or vasoconstriction of Relationship between stroke volume and systemic vascular resistance. In an individual with normal left ventricular (LV) arterial blood vessels function, increasing systemic vascular resistance has little effect on stroke volume. As the extent of LV dysfunction increases, the negative, inverse relationship between stroke volume and systemic vascular resistance becomes more important (B to A).  *The goal is for the heart to maintain appropriate cardiac output Normal Cardiac Function What medications affect preload, contractility and afterload? Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013. HF Pathophysiology: 3 phases lead to HFrEF 1. Insult – Left Ventricle Damaged Initial event or injury to the heart, such as myocardial infarction, viral myocarditis, or chronic pressure overload (e.g., hypertension) Damage to cardiac myocytes and loss of functional myocardial tissue à Structural changes in the left ventricle, leading to reduced contractility 2. Compensation The heart attempts to maintain cardiac output through compensatory mechanisms. Activation of the sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS) to increase heart rate, contractility, and blood volume Cardiac remodeling: Ventricular dilation and hypertrophy to enhance stroke volume Initially helps sustain cardiac function, but increases myocardial oxygen demand and stress on the heart 3. Decompensation Compensatory mechanisms become maladaptive and can no longer maintain adequate cardiac output Progressive worsening of left ventricular function, leading to symptoms such as dyspnea, fatigue, and fluid retention Onset of clinical heart failure with signs of congestion, reduced exercise tolerance, and increased risk of hospitalization Compensatory Mechanisms in HFrEF Compensatory Beneficial Effects Detrimental Effects Response Increased preload through Optimize stroke volume via Frank- Preload reserve exhausted resulting in pulmonary sodium/water retention (via Starling mechanism and systemic congestion RAAS system) Vasoconstriction Maintain BP despite reduced CO; Increased myocardial oxygen demand (MVO2) shunt blood to essential organs Increased afterload further activating such as the brain and heart compensatory responses Tachycardia and increased Maintains CO Increased MVO2 contractility via sympathetic Shortened diastolic filling time (worsens preload) nervous system Precipitation of ventricular arrhythmias B1 receptor downregulation, decreased sensitivity Increased risk of cardiac cell death Ventricular hypertrophy and Maintain CO Diastolic dysfunction remodeling Reduces myocardial wall stress Systolic dysfunction Decreases MVO2 Increased risk of ischemia and cardiac cell death Increased arrythmia risk Fibrosis Modified from Dipiro JT, et al. 10e. Table 14-2 Pharmacotherapy targeted at modifying this neurohormonal activation slows the progression of HFrEF and improves survival. Which drug classes reduce neurohormonal activation and cardiac remodeling? Cardiac Remodeling and Neurohormonal Model Over time, chronic activation Heart failure pharmacotherapy with leads to cardiac remodeling reverse remodeling effects and progressive dysfunction Norepinephrine and epinephrine: beta- blockers LV becomes more spherical, Angiotensin II and aldosterone: ACEi, ARBs, dilates, and hypertrophies and aldosterone antagonists RV dilates and may hypertrophy Natriuretic peptides: ARNI https://www.nejm.org/doi/full/10.1056/NEJMra021498. Accessed April 4, 2020. DOI: (10.1152/ajpcell.00143.2024)