Pathophysiology of heart failure

WHAT IS HF?

WHAT IS HF?

impairment of ventricular filling or ejection of blood

HF in turn leads to the cardinal clinical symptoms of ________&________ and signs of HF, namely edema and rales

dyspnea and fatigue

______is the volume of blood (liters) pumped from ventricles per time (minutes)

cardiac output (CO)

Heart Rate BPM Affected by:

Autonomic innervation

Hormone regulation

Fitness level

Age

STROKE VOLUME (L) Affected by:

•Preload

•Afterload

•Contractility

•Heart size (gender)

•Fitness level

Age

CARDIAC OUTPUT  =

HEART RATE (BPM) X STROKE VOLUME (L)

Preload “stretch”

•Volume of blood inside ventricles during diastole

•Quantify: left ventricle end-diastolic volume (LVEDV or EDV)

•Average adult male at rest: 120 mL

preload

end of diastole

afterload

resistance needed to overcome to force blood out

EF

% of blood being pumped out

Afterload “squeeze”

•Resistance ventricles must overcome to force blood into systemic circulation

•Quantify: systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), end-systolic volume (ESV)

Average adult male at rest: 50 mL

Contractility “strength”

•Contraction of the myocardium through the actin-myosin cross bridge cycle

•Quantify: ejection fraction (EF)

•EF = EDV – ESV à “stroke volume”

                 EDV

•Average adult male at rest: 50-70%

Preload “stretch” Affected by:

•Heart rate

•Ventricle compliance

•Atrial contraction

•Venous/aortic pressure

Total blood volume

Afterload “squeeze” Affected by:

•Aortic pressure

•Systemic vascular resistance

•Ventricle wall thickness

•Ventricle radius

Contractility “strength” Affected by:

•Sympathetic nervous system

•Heart rate

•Ca²⁺

•Rhythm

WHAT IS AN AVERAGE CO FOR AN ADULT MALE? CO = HR x SV

-70bpm * (70ml/1000)=4.9L/min

Average adult CO: 4-8 L/min at rest

What about Cardiac Index? (BSA of 1.9 m²)

Average adult CI: 2.5-4.0 L/min/m² at rest

-CO/BSAà4.9L/min/1.9m2=2.6L/min/m2

preload looking at LVEDPàhow much LV is filled at end of diastole. If you increase the LVEDP, it will _______stroke volume ànot exactly how our body works bc of hemodynamics. If u were to keep filling the heart, it would burst bc there’s a finite amount of volume u can put in the heart

increase

how much blood going out in reality is going to be dependent on how ________ is, how much EP ur blood is releasing at one point.

high ur BP

a scenario lets say u have low BP, so decrease afterload but keep same amount of volume. The SV is going to increase bc _______

it doesn’t have resistance.

Whats happening w/ HF over time is you have very weak ventricles and ur body is trying to compensate by increasing how much is being filled in there, but bc ventricles are weak u have _______ contractility

Decrease

another compensatory mechanism is high BP. Doesn’t matter if u put in a whole bucket of blood. If something is smacking the blood from coming out and it can’t squeeze to go out, the volume _______

won’t change at all

in HF, do a right heart cathàgoing thru inferior vena cava (sometimes superior VC) but going thru a vein. Both of the veins dump into _________ and these pressures are very important bc we can figure out what the underlying problem is in our patients w/ HF

right atria

high on both sides of the heart usually signs of _______à blocked up left side and has no where to go, so starts overfilling onto other side

acute decompensated HF

WHAT CAN IMPACT INTRACARDIAC PRESSURES?

•Heart failure (hypervolemia)

•Pulmonary arterial hypertension

•Pleural effusion

•Cardiac tamponade

•Hypovolemia

•Shock

•Systolic failure (heart contraction) HF with reduced ejection fraction

HFrEF

•Diastolic failure (heart relaxation) HF with preserved ejection fraction

HFpEF

Types of HF Course of disease

•Acute (congestive/decompensated)

•Chronic

Types of HF Location of disease

•Right sided (left-sided HF is most common cause)

•Left sided

•Biventricular

HFREF works

•Loss of intrinsic contractility

•Overstretched ventricles

•Weak and thin ventricles

•Pumping (systolic) dysfunction

HFPEF works

•Failure of ventricles to relax properly

•Thick and stiff ventricles

•Reduced ventricle volume in diastole

•Filling (diastolic) dysfunction

Classification of HF Based on the ejection fraction of the_______

left ventricle

midrange/mildly reduced

HFmrEF

-just bc you have HFpEF, doesn’t mean you will never have HFrEF but u cannot go from ________ bc those are 2 separate problems

HFrEF to HFpEF

What can cause an acute decrease in cardiac output?

-decr HR – bradycardia

-decr in volume –hypovolemia

-incr in BP-HTN

-arrthymias can decr output

-ACS

-medications

-shock

CARDIOMYOPATHY

An acquired or inherited disease of the myocardium associated with mechanical or electrical disfunction, leading to an enlarged/rigid heart muscle

Cardiomyopathy doesn't mean _____ (BUT can be an etiology for it)

HF

w/ non-_____________, there are are issues that are not directly affecting the heart but are going to impact it overtime (ex. obesity)

ischemic cardiomyopathies

COMMON ETIOLOGIES BY TYPE OF HF: HFrEF

CAD/ACS

HTN

COMMON ETIOLOGIES BY TYPE OF HF: HFpEF

HTN

-w/ CAD/ACSà w/ an infarct have ______, tissue is going to get weak and stretched out

tissue dying

HTN more of a cause w/ HFpEF bc if u have a very high pressure system the heart ventricles have to get stronger to overcompensate for thatànot going to actually over-compensate, its just going to make ______so less volume can go in. Body thinks it’s helping out but acc doing more damage in long run

ventricles thicker/stiffer

_________ is the most common cause of HFrEF, accounting for up to 75% of case

Coronary artery disease

The cause of _______ can be singular, multifactorial or unknown

heart failure

HFREF PATHOPHYSIOLOGY

1.SNS: neurohormonal activation

2.Frank-Starling mechanism

3.RAAS: neurohormonal activation

4.Ventricular hypertrophy and remodeling

COMPENSATORY MECHANISMS

•Initiated by acute reductions in BP or reduced renal perfusion (due to low CO)

•Purpose is to provide short-term support to maintain circulatory homeostasis (a normal cardiac output)

•Long term activation results in functional, structural, biochemical, and molecular changes in the heart 

•Further stress results in deterioration of ventricular function

SNS ACTIVATION ↓ in CO causes _______ which decrease parasympathetic tone

unloading of baroreceptors

SNS ACTIVATION ↑ in sympathetic tone which releases __________, and arginine vasopressin (AVP)

norepinephrine (NE), renin

SNS ACTIVATION ↓ β1 receptor sensitivity, ___ stimulation overtime

reduces

Neurohormones:

•NE: ________

tachycardia, vasoconstriction, contractility

Neurohormones:

AVP & Renin: ________

vasoconstriction, water retention

CARDIOMYOCYTE CONTRACTION

•↑ HR, ↓ diastole time, ↑ intracellular Ca²⁺

•↑ actin-myosin interaction, ↑ rate of contraction

•↓ lusitropy (ability to relax)

•Creates greater filament interaction during systole (force), ↑ wall tension

Decreased output alerts the kidney due to ______, kidneys think there is not enough blood volume, activates RAAS

reduced perfusion

RAAS ACTIVATION Neurohormones

Angiotensin II:

•Binds to AT1 receptor, releases AVP and ET-1 and releases NE

•Promotes sodium retention, free water retention, and stimulates aldosterone release

•Vasoconstriction of efferent glomerular arteriole maintains renal perfusion pressure

RAAS ACTIVATION Neurohormones

Aldosterone:

•Increased due to stimulation of the adrenal cortex by angiotensin II , not cleared as well due to decreased hepatic clearance from reduced hepatic perfusion

•Promotes sodium retention and water retention

•Causes interstitial cardiac fibrosis by increasing collagen deposition in the extracellular matrix

KALLIKREIN-KININ SYSTEM Cross talks with RAAS to cause _______

vasodilation

__________ increases release of other vasodilatory molecules (NO, PGI2, EDHF)

Bradykinin

in HF, heart is trying to stretch out, increase the _____, but if actual ventricle is weak and it cannot contract, it doesn’t matter. The amount of blood its going to pump out will still not be good

volume

causes an increase in LV volume and pressure (preload)

Fluid retention

Sarcomeres are stretched and force of ______ is enhanced

contraction

Frank starling mechanism: preload can only be increased to a certain point before it causes ______

congestion

__________ released from the ventricle in response to pressure/volume overload

Purpose is to promote natriuresis/diuresis and inhibit RAAS and SNS

-only natural response from ur body that is good

Natriuretic peptides (NP)

Natriuretic peptides

Atrial NP (ANP):

high affinity, short half life

Natriuretic peptides

Brain or B-type (BNP):

lower affinity but longer half life

Natriuretic peptides

N-terminal (NT-proBNP):

biologically inactive, longest half life

in HF, when u have that vasoconstriction and u have a ton of volume, ur heart releases natriuretic peptides that cause _______à trying to get rid of volume

diuresis

use BNP and _______ (BNP precursor)

NT-proBNP

-important to get _________ if u can to know if its elevated bc of renal failure, Afib, or HFà not perfect biomarker but can trend it to see if its getting worse

baseline BMP

_______change in myocardial cells causing change in size, shape, structure and function of heart

VENTRICULARREMODELING

Which biomarkers are involved with each of the compensatory mechanisms in HF?

SNS

epinephrine

calcium

arginine Vasopressin

Which biomarkers are involved with each of the compensatory mechanisms in HF?

RAAS

renin

aldosterone

angiotensin I/II

Which biomarkers are involved with each of the compensatory mechanisms in HF?

Frank Starling

Natriuretic peptides

ANP

BNP

Which biomarkers are involved with each of the compensatory mechanisms in HF?

ventricular Remodeling

cytokines

Increase preload volume

(Frank-Starling)

benefit:

increase stroke volume (CO)

Harm:

Pulmonary and systemic congestion (edema)

Myocardial O2 demand

Vasoconstriction

(RAAS - Neurohormonal Activation)

benefit:

increase SVR to increase BP

Shunts blood to vital organs (CO)

harm:

increase Myocardial O2 demand

decrease stroke volume (activates compensatory mechanism)

Tachycardia/Increased contractility

(SNS - Neurohormonal Activation)

benefit:

increase HR (CO)

harm:

increase Myocardial O2 demand

decrease Diastole time (less volume)

increase Risk of arrhythmias

increase Myocardial cell death

decrease Β₁ receptor regulation

Ventricular Remodeling

(Hypertrophy)

benefit:

increase CO

decrease myocardial wall stress

decrease myocardial O2 demand

harm:

Diastolic/Systolic dysfunction

increase myocardial cell ischemia/death

increase fibrosis and arrhythmias

AMYLOID CARDIOMYOPATHY PATHOPHYSIOLOGY

•Over 30 proteins attributable to amyloidosis

•Most common protein is transthyretin (TTR)

•Deposition of abnormal proteins into the extracellular space of the myocardium

•ATTR-CM can be inherited (ATTRm-hereditary mutant) or part of the aging process (ATTRwt - wild-type)

•Commonly causes HFpEF

•Novel drug therapy to target TTR protein

HYPERTROPHIC CARDIOMYOPATHY (HCM) PATHOPHYSIOLOGY

•Most common genetic cardiac disease

•Commonly causes HFpEF

•Myosin protein defects are most often observed

•Mutant sarcomere genes trigger myocardial​ changes

•Leads to hypertrophy and fibrosis

_________ are common causes of HF with specific pathophysiology that do not respond to standard HF treatment

ATTR-CM and HCM

DIFFERENTIAL DIAGNOSIS

Dyspnea

•Chronic lung disease

•Pulmonary arterial hypertension

•Anemia

•Pulmonary embolism

DIFFERENTIAL DIAGNOSIS

Edema

•Venous insufficiency

•Nephrotic syndrome

•Deep vein thrombosis

•Lymphedema

DIFFERENTIAL DIAGNOSIS

Jugular venous distention

•Constrictive pericarditis

•Pericardial effusion

•Pulmonary embolism

•Tension pneumothorax

SYMPTOMS OF HF

F:

A:

I:

L:

fatigue

abdominal pain, appetite loss, anorexia

impaired memory (confusion)

lower ability to exercise/do daily activities

SYMPTOMS OF HF

U:

R:

E:

urination at night (nocturia)

respiration issues (dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, cough

edema (pulmonary, lower extremities, hepatic)

SIGNS OF HF

H:

E:

A:

R:

T:

hepatomegaly, hepatojugular reflux

edema (pulmonary/peripheral)

ascites

regurgitation (mitral), S3 gallop

tachypnea, tachycardia

SIGNS OF HF

C:

M:

P:

cool extremities, cardiomegaly, cachexia

mental status changes

pulmonary rates, pleural effusion, positive JVD

Why are these signs/symptoms occurring?

Class 1

Limitation of Physical Activity

None

Clinical Assessment

Ordinary physical activity does NOT cause undue fatigue, dyspnea, palpitations, or angina

Class II

Limitation of Physical Activity

Mild

Clinical Assessment

Comfortable at rest, ordinary physical active may cause symptoms

Class III

Limitation of Physical Activity

Moderate

Clinical Assessment

Comfortable at rest, less than ordinary physical activity leads to symptoms

Class IV

Limitation of Physical Activity

Severe

Clinical Assessment

Symptoms present at rest and worsened with any activity

Stage A At Risk

No objective evidence of cardiovascular disease and no symptoms or limitations in ordinary physical activity

Stage B Pre-HF

No symptoms/signs of HF, but objective evidence of cardiovascular disease

Stage C Symptomatic HF

Structural heart disease with current or previous signs/symptoms of HF

Stage D Advanced HF

Marked HF symptoms interfering with daily life and with recurrent hospitalizations

Who is “at risk”?

HTN, CVD, DM, obesity, hereditary cardiomyopathies, exposure to cardiotoxins

What is “evidence of CVD”?

structural heart disease, increased filling pressures, OR risk factor(s) AND elevated BNP or persistent elevated cardiac troponin levels (in absence of a competing diagnosis, like ACS, MI)

DIAGNOSTIC TOOLS IN HF: NON-INVASIVE

Echo

•LV size, ejection fraction

•Valve function

•Wall motion abnormalities

•Pericardial effusion

ACUTE DECOMPENSATION OF HF (ADHF)

What  is ADHF?

Acute worsening of chronic HF requiring medical intervention