Heart Failure

• ↑ LVEDP → ↑ SV
• The heart pumps the volume it receives
• (the wall of the ventricle gets stretched more and gets maximum overlap of myosin and actin filaments, and allows more tension generation and increases the SV)

• the ventricular wall tension at end of diastole
• The stretch of myocardial fibers (approximated to LVEDP)

• the ventricular wall tension during contraction (systole)
• Resistance ventricle must overcome in order to eject its contents & that gets approximated by systolic arteriole pressure
• Sometimes afterload is more formally defined as ventricular wall stress that develops during systolic ejection

the strength of contraction

SV/EDV

Δ Volume/Δ Pressure

LVEDV/P = preload  and is influenced by compliance

Preload, Afterload, and contractility

• CO =  HR x SV
• ↑ SV due to ↑ preload ↓ afterload ↑ contractility

• wall stress or tension = pr/2h
• pressure= ventricular pressure
• radius =radius of the ventricle
• h = thickness of ventricular wal
• Ventricle wall stress or tension will increase in response to chronically high pressure (HTN) or increase chamber size.
• Increase wall thickness initially serves as a compensatory role because as that denominator of Laplace equation increases then wall stress/tension decreases because the forces gets distributed over a larger surface area.

Preload= moves up or down from a specific point on the FS curve, not changing the curve itself

Contractilty = shifts the curve up or down (LV function does this as well)

Increased Preload: SV increases, and ESV increases slightly because afterload increases (Vice versa is true)

Preload depends on compliance, so if LV compliance is decreased, (severe LV hypertrophy), the slope of the diastolic filling curve becomes steeper. (Point A to B, bottom curve on the loop).

• ↑afterload = ↓SV slighty (ESV and EDV sightly increase secondarily 
• (vice versa as well)

because more work on part of ventricle needs to be expended in order to overcome the resistance to ejection that’s in place because of the increased afterload

There’s a nearly linearly relationship between afterload and ESV. The ESPVR. The line going up from 1 to 2 to 3. Interdependence among all these variables. When afterload ↑, as a result, ↑ ESV.  That extra volume still in ventricle at systole gets added to normal EDV and so↑preload. So that secondary  ↑preload, because of what that means w/Frank Starling, it will partially offset that ↓SV (caused by initial increase in afterload).

TRUE. Problem w/patient in HF, for them the EDV is pretty much maxed out so an increase in afterload that will significantly reduce SV.

usually, ↑afterload →↓SV →↑ESV which is added to EDV and FS kicks in to partially offset the initial decrease in SV caused by increased afterload

↑inotropy = ↑SV (↓ESV and EDV secondarily ↓ a sm. amt) EF increases. (Vice versa is true)

• ESPVR is a function of contractilty
• If contractility increases, the slope of that line goes up, goes from 1 to 2, so in going from 1 to 2 for any given preload and afterload the ventricle is going to empty completely (SV increases) so ESV decreases

Afterload against which the ventricle is contracting and the inotropic state.

But its independent of EDV just prior to contraction.

Afterload & Contractility

NOT preload because LVEDV is preload!

• Impaired myocardial contractility (Ischemic heart disease & Cardiomyopathy)
• Valvular disease
• HTN
• Congenital heart disease
• Diseases of the pericardium
• Pulmonary HTN (cor pulmonale)

• Forward failure (systolic): when heart can’t pump blood forward at whatever rate needed to meet metabolic demands.(failure to maintain good EF)
• Backward failure (diastolic): if the heart can only pump blood if cardiac filling pressures are abnormally high
• Both can also occur.

• Advanced AS
• Uncontrolled severe HTN

• LV hypertrophy
• Restrictive cardiomyopathy
• Myocardial fibrosis
• Transient myocardial ischemia (could be sys too)
• Pericardial constriction or tamponade

Trick Question. In US about 50% of patients fall into each category

LV failure!

d/t aging of population and a lot of interventions that prolong survival, see more people along continuum that we would have before.

• CAD (myocardial infarction or transient myocardial ischemia)
• Dilated cardiomyopathy (DCM)
• Chronic pressure overload (AS & Chronic HTN)
• Chronic volume overload (Regurgitant valve  lesions & High output failure)

but the loss of contractility can be from destruction of myocardial cells (completely destroyed or not functioning normally) and there may be fibrosis

• Higher risk for conduction defects because of abnormal myocardial cells
• LBBB is common
• Because of the problem w/conduction system, ventricular arrhythmias patient w/systolic HF are at high risk for sudden death.

• Systolic HF. The line, ESPVR, shifts down from 1 to 2 so that systolic emptying stops at higher than normal ESV.
• Ventricle trying to contract but can’t contract all that volume. So more volume is left in ventricle at end of systolle and ↓SV, when the normal blood returning from the pulmonary venous system gets added to ↑ESV we now have a higher than normal EDV (moving to right) this increases preload and according to frank starling, would cause an increase in SV. But problem is now we have defect in contractility, normal compensatory mechanism isn’t effective and we end up w/increased in ESV to an increase EDV that backs up into LA and pulmonary veins causing pulmonary congestion

• Diastolic HF
• The prevalence of this type increases w/age, more than 50% of patient over age 70 have diastolic HF.

Impaired relaxation & ↑ stiffness of ventricular wall

**Relaxation is also an active process (energy dependent process).

• Transient or chronic defect
• Acute MI (transient inhibition of energy delivery & diastolic relaxation)
• LV hypertrophy, Fibrosis,  &Restrictive cardiomyopathy (keeps LV walls chronically stiff and unable to relax)
• Pericardial diseases (tamponade), pericardial constriction of some sort that externally limits filling. Pressure from outside the heart, nothing wrong w/ventricle wall of heart itself.

Diastole failure: the LV fills in higher than normal pressure (shift up from 1 to 2). So a patient w/diastolic dysfunction show signs of vascular congestion because that EDP gets transmitted up to LA and pulmonary veins and over to systemic veins as well.

• Class 1 – abnormal LV relaxation with normal LAP
• Class 2, 3, 4 – abnormal relaxation plus decreased LV compliance →↑ LVEDP (When this happens chronically, the LAP ↑ in a compensatory way, because ↑LAP that allows for ventricular filling even though the pressure within the LV is increased itself)

• ischemic heart disease
• longstanding essential HTN
• progressive AS

women are more affected than men for diastolic HF

• diastolic: frequently elderly
• systolic: 50-70yrs

• Diastolic: frequently females
• Systolic: more likely male

• Diastolic: presevered (≥40%)
• Systolic: depressed (≤40%)

• diastolic: usually normal
• systolic: usually dilated

BOTH have congestion and/or cardiomegaly

• Diastolic: S4
• Systolic: S3

• Diastolic: +++
• Systolic: ++

• Diastolic: +
• Systolic: +++

• Diastolic: +++
• Systolic: +

Diastolic (++)

Systolic (0)

EQUAL IN BOTH! (++)

Diastolic (++)


Systolic (0)

• Diastolic: (+) usually paroxysmal
• Systolic: usually persistant

• Results in progressive LV remodeling. The remodeling leads to a ↓ EF, dilation w/arrhythmias, progressive HF and premature death likely.
• Non-cardiac factors (like SNS stimulation, vasoconstriction, Na retention by the kidneys) that can be stimulated by LV dysfunction and then contribute to LV remodeling that goes on. Also contribute to symptoms like dyspnea, fatigue, all characteristic of CHF.

• Change in Sx requiring emergency treatment
• Sudden ↓ CO → ↓BP but no signs of peripheral edema

• Worsening chronic failure
• New-onset (Valve rupture, Large MI, Hypertensive crisis)
• Terminal heart failure

• Present in patients with long-standing heart disease
• BP usually maintained but venous congestion

• Cardiac causes (Left HF, PV stenosis, & RV infarction)
• Pulmonary parenchymal diseases (COPD, Interstitial lung disease (sarcoid), ARDS, &Chronic lung infection)
• Pulmonary vascular diseases  (Pulmonary embolism, Primary pulmonary HTN)

RIGHT (PVR is relatively low)

acute pulmonary embolism

increased ventricular pressure and subsequent accumulation of fluid upstream from affected ventricle

• increased ventricular afterload from some sort of pulmonary disease
• If RV disease develops from primary pulmonary process that’s what’s called Cor Pulmonale and that can lead to RV failure.

Peripheral edema and congestive hepatomegaly

• CAD, cardiomegaly, HTN, valve disease, and pericardial disease.
• CO may be essentially normal at rest but doesn’t respond adequately during stress.

• anemia, pregnancy, AV fistulas, severe hyperthyroidism.
• In this case the ventricle fails because of increased HD burden and also often direct myocardial toxicity possibly by thyrotoxicosis and myocardial anoxia from anemia.

• Frank Starling
• Ventricular remodeling
• Neural hormonal changes (SNS, etc.)

• If HF severe, contractile markedly depressed, curve may be almost flat.
• So any augmentation of CO because of preload is somewhat decreased in its ability to help the situation and of course that additional volume gets reflected back into LA and lungs and pulmonary congestion results. Moving up on the curve will further increased in EDV will just lead to pulmonary congestion

• Increased muscle mass is stiff and less compliant.
• So initial benefits come at the expense of higher than normal diastolic pressure (LVEDP), and again back up in LA, pulmonary veins, and so on.

• Adrenergic Nervous System
• Renin-Angiotensin-Aldosterone System
• ADH
• Natriuretic Peptides
• Other Peptide

• Increase systemic vascular resistance which will help maintain perfusion to vital organs even in setting of decreased CO.
• (BP = CO x total peripheral resistance) so help to balance & maintain BP in early stages of HF.
• These neurohormonal changes will also result in Na & H20 retention, ↑ intravascular volume and preload, goes to maximize SV (FS)

These neural hormonal changes are acutely beneficial but often harmful to failing heart and ultimately contribute to a more progressive downhill course.

• ↓CO gets sensed by baroreceptors in carotid sinus and the aortic arch.
• (sense ↓ BP, so ↓rate of firing, a signal goes to vasomotor control center in medulla, & get a sympathetic discharge and a ↓  parasympathetic tone).
• ↑HR, ↑ contractility, (which ↑ CO)
• and vasoconstriction from alpha stimulation.
• If we get venoconstriction, ↑venous return, ↑preload, ↑ SV (FS).

• Works as long as heart is able to function on ascending part of curve, if we get on flat part of curve, its’ not going to help SV.
• So constriction can be venous or arteriolar. Arteriolar will increase SVR. That will help maintain perfusion pressure and direct circulation to vital organs (heart and brain) at the expense of things like the skin.

• Activated early in patient w/HF.
• Stimuli for renin secretion:
• 1) (juxtaglomerular cells in kidney) ↓renal artery perfusion pressure from low CO
• 2) ↓Na delivery to macula densa (because of altered HD within the kidney ↓ perfusion)
• 3) Direct stimulation of beta 2 receptors in kidney by the activated SNS.

• Renin secreted, goes though RAAS
• Angiotensin II is potent vasoconstrictor, ↑
• resistance and helps maintain BP.
• Angiotensin II also does a few things to ↑
• IV volume : 1. Hypothalamus, stimulate thirst so ↑H2O intake 2.↑ aldosterone secretion from adrenal cortex, which causes Na and H2O reabsorption.
• ↑ preload, (FS),↑CO.
• IF patient is on ascending part of the curve

• Baroreceptors sense, and then send signal. Release ofADH causes water pores to be inserted, ↑ water reabsorption from renal tubules, again ↑ preload and CO.
• Also it’s a vasoconstrictor and that will ↑BP.
• Initially good. But result in adverse consequences. Patient in HF don’t’ want retaining water so eventually these things become counter productive

• Hormones secreted in HF (ANP & BNP).
• The action of these hormones (mediated by specific receptors) is opposite to the other hormone systems that get activated.
• Result in excretion of Na and water, vasodilation, inhibition of renin, and they’re antagonistic to the effect of angiotensin II on aldosterone and vasopressin levels.
• Helpful but not enough to overcome the deleterious effects of the other hormones.

• ANP is stored in atrial cells, released from atrial distention.
• BNP is not detected in normal hearts but is produced when myocardium of the ventricle is subjected to stress of some sort (like HF or MI) relationship between serum BNP levels and clinical severity of HF.

• Endothelin I = potent vasoconstrictor
• Comes from endothelial cells that line all the blood vessels.
• In HF patients, the plasma concentrations of Endothelial  will correlate w/severity of disease and w/adverse outcomes.
• Develop some drugs to try and offset the effects of endothelin but long term benefits haven’t been demonstarted yet

• Cell necrosis
• Apoptosis

• Myocardial infarction
• Cardiotoxic drugs (Doxirubicin)

• Programmed cell death (genetic instructions that will activate various pathways in the cell that will cause cells to fragment and undergoes phagocytosis from other cells without a preceding inflammatory response)
• Triggers include: ↑ catecholamines, Angiotensin II, Inflammatory cytokines, & Mechanical strain from wall stress.

TRUE. (ultrastructural and molecular level)

All of this neurohormonal activation and inflammatory cytokines are believed to alter the genetic expression of the contractile proteins (those ion channels)  & receptors, that are important in the excitation retraction coupling. So they alter the energy production involved w/excitation contraction coupling.

• Decreased ability to maintain Ca+ homeostasis
• Changes that occur in both production and energy utilization (ATP).
• Not completely clear how it all fits in, it’s an area of current research

• 1. Increased metabolic demands (Fever, infection, anemia, ↑HR, pregnancy, hyperthyroidism)
• 2. Increased circulatory volume (↑ preload d/t ↑Na intake, administer too much IVF, & renal failure)
• 3. Conditions that increase afterload (uncontrolled HTN and PE)
• 4. Conditions that impair contractility (neg. inotropes, MI, chronic alcohol abuse)
• 5. Failure to comply with medication regime
• 6. Excessive bradycardia

• Symptoms:
• Dyspnea
• Orthopnea
• Paroxysmal nocturnal dyspnea
• Fatigue

• Clinical Findings:
• Diaphoresis
• Tachycardia, Tachypnea
• Rales
• Loud P2 (pulmonic component of S2)
• S 3 gallop (systolic dysfunction)
• S 4 gallop (diastolic dysfunction)

• Symptoms:
• Peripheral edema
• RUQ discomfort (from hepatic enlargement)

• Clinical Findings:
• JVD
• Hepatomegaly
• Peripheral edema

• Altered or dull mental status (from ↓ cerebral perfusion)
• ↓u/o from ↓ renal blood flow
• Nocturia (blood flow redistributed to kidney in supine position)
• Fatigue because less flow to skeletal muscles, patient feels weak and fatigued.

Severe breathlessness wakes patient up from sleep, from fluid reabsorption d/t supine position (usually 2-3 hrs after falling asleep)

• CXR shows upper zone vascular redistribution.
• The vessels supplying the upper lobes are larger than those supplying the  lower lobes.
• Edema is more prominent in lung bases, where hydrostatic pressure is highest

• Short linear markings in periphery of lower lung fields and indicate intralobar edema.
• Show up when LAp exceeds about 20mmHg and represent interstitial edema.
• Can progress (if Lap exceeds 25-30) can be opacity of air spaces.

There’s often increased lymphatic drainage, Relationship w/LAp and CXR findings is somewhat altered or attenuated in the patient w/chronic HF.

12

• Plasma BNP levels of less than 100 = HF unlikely.
• If level is between 100-500 = intermediate probability for HF
• If level is above 500 = consistent w/diagnosis of HF.

• I: No limitation of physical activity
• II: Slight limitation of activity. Dyspnea & fatigue with moderate exertion (i.e. walking upstairs quickly)
• III: Marked limitation of activity. Dyspnea
• with minimal exertion (i.e. slow walking upstairs)
• IV: Severe limitation of activity. Symptoms
• are present even at rest

because severity symptoms has excellent correlation w/survival and quality of life.

• A: Patient who is at risk of developing heart failure but has not yet developed structural cardiac dysfunction (i.e. patient with CAD, HTN, or family history of cardiomyopathy)
• B: Patient who has structural heart disease associated with heart failure but has not yet developed symptoms
• C: Patient who has current or prior symptoms of heart failure associated with structural heart disease
• D: Patient who has structural heart disease and marked heart failure symptoms despite maximal medical therapy and requires advanced interventions (i.e. cardiac transplantation)

45-60%

40%

refractory; ventricular

• They actually have similar rates of hospitalization, in hospital complications and mortality.
• Systolic is not necessarily worse in this case.

• ↑BUN & creatinine levels
• ↓ Na and ↓ K levels
• High BNP
• Severely depressed EF
• Limited exercise tolerance, and often multifocal PVCs.

• 1. Identify & correct underlying cause (Replacing incompetent valve or coronary revascularization, aggressively tx untreated HTN, or d/c alcohol consumption)
• 2. Eliminate acute precipitating factors (Infection or arrhythmia. ↓ Na intake. Maybe medication adjustment. d/c NSAIDS!)
• 3. Symptom management (Na+ restriction, diuretics, promote forward flow w/vasodilators & inotropic support)
• 4. Modulate neuroendocrine response (Limit the progression of remodeling and LV dysfunction)
• 5. Prolong long-term survival

• Relieve the vascular congestion in the pulmonary and peripheral edema ( faster than any other drug) by ↓ preload and EDP.
• ↓hydrostatic force causing pulmonary congestion to begin with.
• Use diuretics carefully so they don’t significantly ↓ SV And CO.
• In HF, on flatter part of curve,so not substantially ↓ SV & CO by ↓ preload.
• If you overly diurese, on steeper part of curve and will effect SV and CO.

• Diuretics that act primarily on loop of Henle (Lasix) are most potent.
• Thiazide (hydrochlorothiazide) are useful but less effective especially in setting of decreased renal perfusion.

Diuresis can also cause electrolyte abnormalities (low K and low Mg) can cause arrhythmias in patient already prone to arrhythmias.

• Venous dilators, ↑ venous capacitance, ↓venous return & ↓preload.
• Improve the pulmonary congestion as long as patient is on flat part of the curve.
• If patient is on steeper part of curve, venodilation may have too much of impact on HR, SV, CO and BP

• Pure arteriolar vasodilators. ↓ SVR & afterload → ↑ SV & shift curve up.
• Although an arterial vasodilator would ↓BP (don’t want if pt is already hypoTN) this doesn’t usually happen.
• The ↓SVR usually results in an ↑ CO so BP is constant or only slightly decreased.

• ACE I specifically have been found to limit ventricular remodeling. They will improve stamina, ↓ need for hospitalization and extend survival in pt w/HF and ↓ EF.  
• ARB provide more complete inhibition of whole system but not shown to be more beneficial so usually reserved for pt that can’t tolerate ACE I (cough).
• Can get balanced vasodilation if you combine one of the nitrates w/hydralazine but in general the RAAS inhibitors are superior

ACE I

• Shifts curve up to point C.
• For given preload, SV And CO would be increased.
• So drugs useful for patient w/decreased EF but not really effective if EF is already well preserved.

One reason they can only be given IV and another reason continued administration causes down regulation of adrenergic receptors so the effectiveness of the IV administration declines overtime.

Milrinone. It’s limited to treating acute HF because even though it’s given IV (thought there was a promising PO version of the drug but it hasn’t proven to be so promising)

Digoxin is old but still useful. IV or PO. Digoxin improves symptoms but doesn’t really improve long term survival. Also useful if patient is in AF.

• Historically contraindicated because of negative inotropes.
• But new studies say they have some benefit in augmenting CO and improving survival.
• Not clear how it works but maybe decreasing HR is beneficial.
• Also blunting chronic SNS activation that as we know is initially good then not so good.

• Evidence that aldosterone itself contributes to cardiac fibrosis and remodeling.
• Need to follow K carefully, esp. if on ACE I.
• Trials show if patient already taking ACEI and diuretics, and aldosterone antagonist was added, that mortality decreased & symptoms improved.

Anti inflammatory, lipid lowering effect may decrease morbidity and mortality n patients w/systolic failure.

• Failing heart – point “a”
• Diuretics – point “b”(Also venous dilation)
• Inotropes – point “c”
• Vasodilator (balanced or arteriolar) – point “d”
• Inotrope + vasodilator – point “e”

Prevent intracardiac thrombus formation if systolic dysfunction is severely impaired. It is somewhat controversial if not another reason for anticoagulation. But it has been tested in clinical trials. If EF is seriously decreased

Amiodarone

• Particularly indicated if patient has chronic ischemia or non-ischemic cardiomyopathy (dilated) and at least moderately reduced EF (less than or equal to 35%).
• So an ICD may be helpful even if patient doesn’t have arrhythmias because it decreases the likelihood of sudden death in this patient population.

• Patient also have intraventircular conduction defects: L bundle is common. So fact L and R ventricle aren’t coordinate will contribute to cardiac symptoms. So if you can re-coordinate so ventricles contract together, it help can help LV systolic dysfunction.
• Referred to as cardiac resynchronization therapy (appropriate for select patients w/ advance diastolic dysfunction like EF less than or equal to 35% or pt w/prolonged QRS or continued symptoms of failure on maximum drug therapy.

High Risk with no symptoms so lifestyle modification (diet Na restriction, weight control, control blood sugar, reduce alcohol consumption) patient and family education

• Structural heart disease, no symptoms
• Tx HTN, diabetes, dyslipidemia, ACEI or ARBs
• (BB for select patients in the next step)

• ACEI and BB in ALL Patients
• Dietary Na restriction, diuretics, and digoxin
• Cardiac resynchronization (if BBB present)
• Revascularization (MV surgery)
• Consider multi-disciplinary team
• Aldosterone antagonist, nesiritide

• VAD, transplant
• Hospice

• Goals of treatment: Relief of pulmonary & systemic congestion and Address correctable causes (HTN &CAD)
• Treatment: Diuretics. Careful not to under fill LV (it’s stiff and needs higher than normal pressures). So if we excessively diurese, decreased ventricular filling, decreased SV.
• Unlike patients w/impaired systolic function, BB, RAAS-I have not shown mortality benefit. Inotropes don’t’ work because EF preserved

• Prevent development by ↓ing risk factors (Treat CAD, HTN, DM & Weight control)
• Allow adequate LV filling by ↓ing HR (Beta blockers, calcium channel blockers, & digoxin)
• Control volume overload (Diuretics, long-acting nitrates, low sodium diet)
• Restore & maintain SR (Cardioversion, amiodarone, & digoxin)
• Decrease ventricular remodeling (ACEI, statins)
• Correct precipitating factors (AVR, coronary revascularization)

• Previously asymptomatic pt with CAD, severe HTN, or acute valve regurg
• Compensated pt decompensates

• Normalize filling pressures
• Restore tissue perfusion
• Identify appropriate profile for the patient and that helps guide treatment in terms of need for diuretics, vasodilators, and so on

• Profile A: warm & dry 
• Profile B: warm & wet (↑LV filling pressures, congestion)
• Profile C: cold & wet (↑LV filling pressures, congestion, ↓CO, & vasoconstriction)
• Profile L: cold & dry ( ↓CO, & vasoconstriction)  but don’t have signs of vascular congestion. So this patient may be volume depleted or have limited cardiac reserve but in the absence of volume overload.

• Cause is cardiac in origin pulmonary edema (As opposed to negative pressure pulmonary edema)
• Can appear suddenly in asymptomatic patient

• left-sided heart failure↑ capillary hydrostatic pressure →fluid accumulation in interstitium & alveolar spaces
• If LVEDP > 25 mmHg if normal oncotic pressure

• Hypoxemia due to shunt
• Severe dyspnea & anxiety
• Profiles “B” & “C” (Frothy sputum, Rales & wheezes)
• (Cold clammy increased SNS stimulation = profile C)

• Lasix (↓preload→↓PCWP)
• Morphine (↓anxiety & ↓venous return)
• Nitrates (NTG)
• Oxygen (via FM)
• Position (↑HOB to↓venous return)

*also inotropes*

yes

• Improve oxygenation
• Eliminate underlying cause

Mechanical devices – IABP, LVAD

Heart Failure!!! Wouldn't do elective surgery on someone in CHF or acute pulmonary edema

• D/C diuretics day of surgery
• Continue beta blockers (BB decrease morbidity and mortality)
• D/C ACEI/ARB --controversial.Can usually be d/c day of or day before.  Increased risk of intraoperative hypotension. ACEI-given to decrease risk of ventricular remodeling in HF and prevent renal dysfunction in diabetic pt, stopping for 1 day won’t have huge impact on that.
• Digoxin-continue day of surgery.
• All lab tests, particularly electrolytes need to be carefully evaluated.

• Adjust drug dosing
• Opioids beneficial – inhibition of adrenergic activation
• Positive pressure ventilation & judicious PEEP improves oxygenation
• Monitor according to complexity
• Regional + OK
• Additional cautions with transplanted heart

• long term immunosuppression
• The transplanted heart is denervated, increased HR can only be achieved w/direct acting beta agonist like Epi.

• Treat pain aggressively
• Restart usual meds ASAP