University:
West Coast University
Course:
PHAR 740 | IPC Cardiopulmonary and Renal III
Academic year:

2024
Views:

139

Pages:

19
Author:

Asal A.

Pathophysiology of Heart Failure Adam Kassan, PhD Associate Professor, Pharmaceutical Sciences West Coast University, School of Pharmacy akassan@westcoastuniversity.edu 323-454-5071 Spring 2023 Heart Failure: Definition • Heart failure is present when  heart is unable to pump blood at a sufficient rate to meet the metabolic demands of the body (CO) • Most commonly results from impaired left ventricular function CO: Cardiac Output Heart Failure: Introduction • Heart failure results in clinical syndrome of Edt  fatigue, shortness of breath, volume overload • The final and most severe manifestation of nearly every form of cardiac disease  including coronary atherosclerosis, MI, valvular diseases, hypertension, congenital heart disease, and cardiomyopathies Heart Failure: Introduction • ~1 million new cases each year in the US  ~6.5 million with HF  ~400.000 deaths/year • Accounts for >12 million medical office visits annually  the most common diagnosis of hospitalized patients aged ≥65  grave prognosis o mortality rate at 5 years ~50% HFSA: Heart Failure Society of America CDC: Centers for Disease Control and Prevention Heart Failure: Introduction • 2 classes  Chronic compensated heart failure o often termed congestive heart failure (CHF)  Acute decompensated heart failure (ADHF) o exacerbation of CHF, often multifactorial in etiology - ischemia, MI, dietary indiscretion Determinants of Contractile Function in the Intact Heart otfEEIgoge es • CO = HR × SV • Determinants of the stroke volume  contractility  preload backto  afterload hypertension lopinresistone CO: Cardiac Output HR: Heart Rate SV: Stroke Volume Pathophysiology of Heart Failure • Heart failure may result from a variety of cardiovascular insults • The etiologies can be grouped into those that cause:  systolic dysfunction contraction o impaired ventricular contractility o increased afterload  diastolic dysfunction o impaired ventricular relaxation and filling Fy Pathophysiology of Heart Failure • Many patients demonstrate both systolic and diastolic abnormalities • Categorize heart failure based on left ventricular ejection fraction (LVEF)  HF with reduced EF (HFrEF) o primarily systolic dysfunction  HF with preserved EF (HFpEF) o primarily diastolic dysfunction Heart Failure with Reduced EF (HFrEF) • Diminished EF due to systolic dysfunction  impaired myocardial contractility  or excessive afterload • In decreased cardiac contractility  ESPVR is shifted downward  ↑ESV • Venous return is added  ↑EDV (preload)  compensatory function by elevating SV via Frank–Starling mechanism  impaired contractility and the reduced EF cause the ESV to remain elevated ESPVR ESV EDV U ESa Imax vote • Normal PV loop (solid line) • Systolic dysfunction (dashed blue line) • ESPVR: end-systolic pressure–volume relation • ESV: end-systolic volume • EDV: end-diastolic volume • SV: stroke volume Heart Failure with Reduced EF (HFrEF) • During diastole, elevated LV pressure is transmitted to:  left atrium o through the open mitral valve  and to the pulmonary veins and capillaries • Elevated pulmonary capillary hydrostatic pressure results in: • transudation of fluid into the pulmonary interstitium o symptoms of pulmonary congestion Heart Failure with Preserved EF (HFpEF) • Caused by diastolic dysfunction  increased ventricular wall stiffness o fibrosis • Pressure-volume curve is shifted upward • impaired relaxation as a result of stiffness • ↓EDV • at any diastolic volume, the ventricular pressure is higher than normal • • • • • • Normal PV loop (solid line) Diastolic dysfunction (dashed blue line) ESPVR: end-systolic pressure– volume relation ESV: end-systolic volume EDV: end-diastolic volume SV: stroke volume Heart Failure with Preserved EF (HFpEF) Patients with diastolic dysfunction often manifest signs of vascular congestion because the elevated diastolic pressure is transmitted retrograde to the pulmonary and systemic veins Compensatory Mechanisms in Heart Failure Several compensatory mechanisms that buffer the fall in CO and help preserve sufficient BP to perfuse vital organs • Frank–Starling mechanism • Neurohormonal alterations • Development of ventricular hypertrophy and remodeling Compensatory Mechanisms in Heart Failure Frank–Starling Mechanism • In normal heart, cardiac performance increases as a function of preload • Increased contractility shifts curve upward  augmented stroke volume at any level of preload • In heart failure, the curve is shifted downward Compensatory Mechanisms in Heart Failure Frank–Starling Mechanism • Point a: normal EDV at rest • Point b: same person after heart failure  stroke volume has fallen  ↑EDV o ↑ stretching serves a compensatory role • Point c: further ↑EDV  SV slightly augmented  signiﬁcantly ↑EDP results in pulmonary congestion Compensatory Mechanisms in Heart Failure Neurohormonal Alterations • Adrenergic nervous system  ↑HR  ↑contrac lity  ↑vasoconstric on • RAAS  ↑adrenergic nervous system • Antidiuretic hormone (ADH)  ↑preload and CO Compensatory Mechanisms in Heart Failure Neurohormonal Alterations • Neurohormonal alterations are initially beneficial • Continued activation ultimately proves harmful  ↑venous return may exacerbate conges ve pulmonary symptoms  ↑TPR will ↑a erload and impair SV and CO  ↑HR augments metabolic demand  continuous sympathetic activation results in a reduced inotropic response (downregulation of β1 receptors)  chronically elevated AngII result in fibrosis and adverse remodeling of the failing heart Compensatory Mechanisms in Heart Failure Neurohormonal Alterations • Natriuretic peptide (ANP, BNP)  natural “beneficial” hormones secreted in HF failure in response to increased intracardiac pressures o excretion of Na+ and water o vasodilatation o inhibition of renin secretion o antagonism of the effects of AngII Compensatory Mechanisms in Heart Failure Ventricular Hypertrophy and Remodeling • Ventricular hypertrophy and remodeling are important compensatory processes • Increased wall stress  development of myocardial hypertrophy (muscle fibers)  maintain contractile force • Increased stiffness  higher diastolic ventricular pressures  transmitted to left atrium and pulmonary vasculature

Pathophysiology of Heart Failure

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