Heart Failure & Remodeling Flashcards
3 etiologies of heart failure
- Imparied ventricular contractility
- Increased afterload
- Impaired ventricular relaxation & filling
Cor Pulmonale
Right sided heart failure caused by a primary pulmonary process
HFrEF
Heart failure with reduced ejection fraction (systolic dysfunction)
Systolic emptying ceases at higher-than-normal ESV; stroke volume falls
Normal venous return is added to increased ESV and so EDV increases as well; this increased pre-load induces a compensatory increase in stroke volume but impaired contractility and reduced EF cause the ESV to remain elevated
Elevated LV pressure is transmitted to the LA via the open mitral valve during diastole and to the pulmonary vein & capillaries resulting in edema
Causes of HFrEF - 3 categories + examples
- Direct destruction of heart muscle (MI, myocarditis)
- Overstressed heart muscle (Tachycardia)
- Volume overload (mitral regurgitation)
HFnEF
Heart failure with normal ejection fraction / diastolic failure
Caused by abnormalities of diastolic relaxation or ventricular filling; ventricular filling occurs at higher pressures; elevated diastolic pressure is transmitted to pulmonary and systemic veins, causing congestion
Ventricle may become hypertrophic in compensation to maintain these higher diastolic pressure
Causes of HFnEF
- High afterload (HTN, aortic stenosis)
- Myocardial thickening / fibrosis (hypertrophic cardiomyopathy)
- External compression (pericardial fibrosis/effusion)
Pathological effects of neurohormonal response to heart failure
- Increased circulating volume may exacerbate congestion
- Elevated arteriolar resistance increases afterload
- Increased HR exacerbates metabolic demand
- Continuous sympathetic activation results in down-regulation of B-adrenergic receptors, decreasing the myocardium’s sensitivity to circulating catecholamines (reduced inotropy)
- Chronically elevated AII and aldosterone stimulate fibroblasts, leading to myocardial fibrosis
Baroreceptor Reflex
BP info is sensed by baroreceptors (stretch-sensitive sensory neurons) in the carotid sinus and aortic arch; these neurons transmit via CN IX to the cardiovascular control center in the medulla; sympathetic outflow from the medulla to the heart is altered
Production of renin
Renin is produced by juxtaglomerular cells in the kidney in response to:
- Decreased renal artery perfusion
- Direct stimualtion by the adrenergic system
Actions of angiotensin II
- Constricts arterioles, raising TPR
- Acts on the hypothalamus, stimulating thirst
- Acts at adrenal gland to increase aldosterone secretion
Aldosterone
Promotes Na+ reabsorption from the kidney
Anti-Diuretic Hormone (ADH) (Vasopressin)
Secreted by the pituitary
Promotes water retention in the distal nephron
Atrial Natriuretic Peptide (ANP)
ANP is stored in atrial cells and released in response to atrial distention; ANP binds at natriuretic peptide receptors (NPRs) whicha re receptor guanylate cyclases that produce cGMP; cGMP activates SERCA to stimulate Ca2+ uptake, thereby reducing cytoplasmic Ca2+ levels, causing:
- In the kidneys - Increased GFR and secretion of Na+ and water
- In VSMCs - Vasodilation
- In the adrenal gland - inhibition of aldosterone and renin release
Role of hypertrophy in heart failure
Heart failure causes chronic elevation of wall stress because of ventricular dilation or the need to generate high systolic pressures in order to overcome excessive afterload
Sustained increase in wall stress stimulates hypertrophy (via LaPlace), which increases wall stiffness and contributes to elevated LV diastolic pressure which are transmitted to the LA, causing pulmonary congestion
Eccentric Hypertrophy
Pathological hypertrophy caused by chronic chamber dilation due to volume overload
New sarcomeres are formed in series with the old, causing myocytes to elongate; radius of the ventricular chamber enlarges in proportion to the increase in wall thickness
Concentric Hypertrophy
Hypertrophy that often results from physiological mechanisms (i.e. exercise) but can also be pathological
New sarcomeres are synthesized in parallel with the old, causing thickening of myocytes; wall thickness increases without a proportional increase in ventricular radius
Orthopnea
Sensation of labored breathing while laying flat, relieved by sitting upright; this is a symptom of heart failure related to increased pulmonary congestion
Due to redistribution of intravascular blood from abdomen and lower extremities toward the lungs after laying down
Paroxymal Noctural Dyspnea (PND)
Severe breathlessness that awakens a patient from sleep after 2-3 hours; this is a symptom of heart failure related to increased pulmonary congestion
Caused by gradual reabsorption of lower extremity interstitial edema into circulation, with subsequent increased venous return to the heart and pulmonary congestion
New York Heart Association (NYHA) Functional Classification of Heart Failure
- Asymptomatic
- Symptomatic with moderate exertion
- Symptomatic with minor exertion
- Symptomatic at rest
ACC/AHA Heart Failure Stages
A. Patient is at risk of developing heart failure
B. Patient has structural heart disease associated with heart failure but is asymptomatic
C. Patient has current or prior symptoms of heart failure associated with structural heart disease
D. Patient has structural heart disease and market heart failure symptoms despite maximal medical therapy; requires advanced intervention
Signs of Left Sided Heart Failure - Low Flow
Cool extremities
Dusky appearance
Tachycardia
Low pulse pressure
Signs of Left Sided Heart Failure - Increased Left Atrial Pressure
Rales Rhonchi/wheezing Hypoxia Tachypnea Orthopnea Paroxymal Noctural Dyspnea
Rales
Created by the “popping open” of small airways during inspiration that had been closed off by the pressure of edema fluid; most prominent at lung bases, where hydrostatic forces are greatest
Rhonchi/Wheezing
Caused by compression of conduction airways by pulmonary congestion
Signs of Right Sided Heart Failure
Systemic Edema
Hepatic congestion with RUQ tenderness
Jugular Venous Distension - an estimation of right atrial pressure
S3 Gallop
S4 gallop
S3 gallop
Caused by rapid expansion of the ventricular walls in early diastole; typical of HFrEF
S1-S2-S3 (Ken-tuc-key)
S4 gallop
Caused by atria contracting forcefully against a stiff or hypertrophic LV
S4-S1-S2 (Ten-ne-ssee)
Upper zone vascular redistribution
Evidence of heart failure seen on chest radiograph; vessels supplying the upper lobes of the lungs appear larger than those supplying the lower lobe
Caused by compression of vessels at the lung bases by lung edema secondary to greater hydrostatic pressure
BNP
Assay for heart failure; BNP levels correlate with degree of LV dysfunction and prognosis with normal BNP < 100
Good negative predictive value - a patient with signs of heart failure but low BNP probably doesn’t have heart failure
Implantable Cardioverter-Defibrillator (ICD)
Indicated for many patients with chronic ischemic or non-ischemic dilated cardiomyopathies with reduced systolic function
Cardiac Resynchronization Therapy (CRT)
Bi-ventricular pacemaker for patients with QRS duration > 120 msec (due to L. bundle branch block) and LV ejection fraction < 35%
Causes the LV lateral and septal walls to contract together, producing an efficient contraction and increased SV
Role of HDAC9 in cardiomyocyte hypertrophy
HDAC9 suppresses hypertrophy in response to stress by deacetylating genes required for hypertrophic growth
Knockout stimulates cardiomyocyte hypertrophy as well as BNP expression; overexpression blocks hypertrophy
Role of HDAC 1/2 in cardiomyocyte hypertrophy
HDAC1/2 deacetylate genes that suppress growth, thereby allowing the heart to grow in response to stress
HDAC1/2 inhibitors are promising drug candidates for treatment of heart failure
Changes in myosin heavy chains seen in cardiac remodeling
Pathological hypertension 2/2 chronic hypertension and aortic valve stenosis is characterized by an increase in the B-B MHC isoform and decreased ATPase activity
Physiological hypertrophy due to exercise or pregnancy is characterized by an increase in the A-A MHC isoform and an increase in ATPase activity
Role of calcineurin in cardiac remodeling
Calcineurin, a Ca2+ dependent phosphatase, targets NFAT; dephosphorylated NFAT move from the cytosol to the nucleus where it acts as a TF for genes related to cardiac remodeling (i.e. B MHC)
