CHF & cardiac remodelling

Question 1

Furosemide MOA

Answer 1

inhibit sodium and chloride reabsorption by competing with Cl for the Na/K/Cl symporter in the ascending limb of the loop of Henle (decrease in intracellular Na, K, Cl)

• also inhibits absorption of sodium and chloride in the proximal & distal tubules)
• increases excretion of calcium, Mg, bicarb, ammonium, phosphate

Question 2

Frank-Starling curve

Answer 2

SV vs LVEDV/P
curve depends on contractility
increase in LVEDP = increase in SV, to some extent

HF: increase LVEDP in order to increase SV

Question 3

Ejection fraction

Answer 3

EF = SV/end-diastolic volume

usually 50-75%

Question 4

Pressure-volume loops for cardiac cycle

Answer 4

a = mitral valve opens (atrial P > ventricular P)
a-b =diastolic filling (slope dependent on compliance)
b = mitral closes
b-c = isovolumetric contraction
c = aortic valve opens
c-d: systolic ejection (vol decreases, but P rises until ventricular relaxation occurs) - pressure at this point = afterload
d = aortic valve closes
d-a = isovolumetric relaxation

b-a = SV

Question 5

Effect of preload on P-V curve

Answer 5

Increase in preload = increase in SV (longer a-b, but also higher slope as pressure increases)

Question 6

Effect of afterload on P-V curve

Answer 6

Increase in afterload = longer isovolumetic contraction (need to reach higher P before ejection)
- lower SV, higher ESV
Relationship between afterload and ESV mostly linear (ESPVR)

Question 7

Effect of contractility on P-V curve

Answer 7

Slope of ESPVR line
Increased contractility - increased slope
Increase in contractility –> higher SV, lower ESV

Question 8

Compensatory response to low CO

Answer 8

Raise HR (reflex tachycardia)
Neurohormonal activation via RAAS and SNS
Ventricular remodelling (concentric for higher pressure, eccentric for higher volume)

Question 9

Cardiac hypertrophy incidence

Answer 9

15% of popn
50% popn with moderate HTN
90% popn with CV disease

Question 10

Concentric hypertrophy

Answer 10

more relative wall thickness
results from P overload
increased LV mass
increased contractility
increased LVEDV (only when dilated)
Length increases by 5%
X-sectional area increases by 150%

Question 11

Eccentric hypertrophy

Answer 11

Less relative wall thickness
Results from V overload
Increased LV mass
Decreased contractility
Increased LVEDV (when dilated)
Length increased by 30%
X-sectional area increased by 50%

Question 12

Qualitative compensation due to increased myocardial workload

Answer 12

Decrease amount of work by SR Ca ATPase
Increase contractile proteins
Increase glycolysis, decrease FA oxidation
Increase cardiac epi/nepi receptors
increasing ANP/BNP expression

Question 13

Pathological hypertrophy

Answer 13

No long term benefit
Interstitial fibrosis
Fetal gene expression increase
Decreased cardiac function over time
Associated with heart failure
Not reversible, unless HTN treated
cardiac work drops significantly after ischemia

Question 14

Heart failure definition

Answer 14

Inability of the heart to pump blood at sufficient rate (low CO) to meet metabolic demands of the body, or to do so at abnormally high filling pressures, or both.

Question 15

Mechanisms of heart failure

Answer 15

Low preload
High afterload
Reduced contractility
Neurohormonal

Question 16

Neural response to low CO

Answer 16

Decreased baroreceptor firing –> increased SNS and decreased PNS
o Increased HR via beta-1 receptors
o Increased ventricular contractility
o Arterial/venous vasoconstriction via alpha receptors (NB, this increases VR too)
o Increase renin release via stimulation of JG beta-1 receptors

Question 17

Hormonal response to low CO

Answer 17

•RAA Axis: Decreased renal artery perfusion pressure due to reduced CO, decreased salt delivery to macula densa, and stimulation of JG beta-1 receptors by SNS  Increased renin secretion from granular cells in JG apparatus  Renin converts angiotensinogen to angiotensin I  Angiotensin I (via ACE)  Angiotensin II
o Vasoconstriction
o Increased intravascular volume by stimulating thirst via hypothalamus, increased aldosterone from adrenal cortex (increased sodium/water resorption at distal convoluted tubule)
o Increased ADH secretion from posterior pituitary – more water resorption by increased water retention in the distal nephron, and systemic vasoconstriction.

Endothelins
Natriuretic peptides - decrease in low CO
o Released in response to increased intracardiac pressure by atrial cells (Mechanoreceptors triggered by stretch, release ANP). Ventricular cells release BNP by the same means.
o Stimulate sodium and water excretion (decreased preload)
o Vasodilation – decreased SVR and increased forward CO (less afterload)
o Inhibition of renin secretion
o Antagonizes effects of angiotensin II (see above)

Question 18

Sx of L-sided HF

Answer 18

exertional dyspnea - pulmonary congestion & decreased forward flow (compress airway, J receptor –> shallow, rapid breathing), accumulation of lactic acid
Dulled mental status
Decreased urine output and nocturia (renal perfusion at night)
Orthopnea
Paraoxysmal nocturnal dyspnea (severe breathlessness 2-3 hours into sleep)
Hemoptysis - rupture of engorged bronchial veins
Fatigue

Question 19

Sx of R-sided HF

Answer 19

Right upper quadrant discomfort (liver engorgement, edema within GI tract –> anorexia and nausea)
peripheral edema

Question 20

Physical signs of HF

Answer 20

Cachexia (frail, wasted appearance)
Diaphoresis due to increased SNS
Cool extremities
Tachypnea
Sinus tachycardia
Pulsus alternans (alternating strong/weak contractions detected peripherally, sign of advanced ventricular dysfunction)
Pulmonary rales: "popping open" of small airways that had been closed off by edema prior to inspiration
Coarse rhonchi and wheezing
Loud P2
S3
S4 may be heard
Mitral regurgitation murmur (valve stretched open)
Parasternal RV "heave"
Tricuspid regurgitation murmur
Elevated JVP
Hepatomegaly
Edema

Question 21

Lab tests for HF

Answer 21

When mean LA pressure > 20 mmHg, Kerley B lines
> 25-30 mmHg, alveolar pulmonary edema
CXR: cardiomegaly, cardiothoracic ratio > 0.5, enlargement of azygous veins
Pleural effusions (more common with bilateral failure)
Ventricular function –> echo, radionuclide ventriculography
Sometimes cardiac cath is necessary –> valvular ischemic etiologies
Elevated BNP - LV dysfunction/prognostic marker
Elevated neurohormonal & cytokine stimulation - prognostic marker

Question 22

Causes of R-sided HF

Answer 22

L failure
Pulmonic valve stenosis
R ventricular infarct
parenchymal pulmonary disease
pulmonary vascular disease

Question 23

Causes of L-sided HF

Answer 23

Loss of contractility (MI, MR, AoR, pathological hypertrophy)
excessive afterload
impaired diastole

Question 24

Systolic dysfunction

Answer 24

Volume buildup in ventricle - elevated pressure

increased back pressure, pulmonary congestion, low CO

Question 25

Diastolic dysfunction

Answer 25

impaired relaxation (secondary to LVH, ischemia, cardiomyopathies) filling at higher P back pressure impaired filling due to obstruction --> no filling --> low SV --> failure

Question 26

Acute heart failure

Answer 26

* Reduced CO * Decreased tissue perfusion * Increased pulmonary congestion/peripheral congestion * Orthopnea/PND * Cough * Increasing abdominal girth (ascites) * Peripheral edema * Fatigue associated with systolic or diastolic dysfunction, valve dysfunction, cardiac rhythm abnormalities * Distressed * Elevated JVP, audible S3, crackles in both fields, tachypnea and tachycardia * MANAGEMENT DIFFERENT FROM CHRONIC

Question 27

Chronic heart failure

Answer 27

* Dyspnea * Orthopnea/PND * Fatigue * Weakness * Exercise Intolerance * Dependent edema * Cough * Weight gain * Abdominal distension * Normal HR/RR * Not distressed * Nocturia * Cool extremities ``` Uncommonly: • Cognitive impairment • Altered mental state from normal • Nausea • Abdominal discomfort • Oliguria • Anorexia • Cyanosis ```

Question 28

Complications of L-sided HF

Answer 28

Pulmonary edema Renal perfusion drop Brain - hypoxic encephalopathy, coma Reduced CO - infarct/ischemia

Question 29

Complications of R-sided HF

Answer 29

``` Hepatomegaly --> congestion Elevated P in portal vein & tributaries Congestive splenomegaly Chronic bowel edema (ascites) Kidney congestion Brain - hypoxic encephalopathy Pleural/pericardial effusion Sub-Q tissues: peripheral edema ```

Question 30

Tx of acute HF

Answer 30

Monitor o Vital signs o Close observation of fluid balance o CVP/Arterial line for Pt who may require pressors/inotropes Investigations o Bloodwork: CBC, electrolytes, BUN, Cr, Glucose, Troponin o CXR o ECG Therapy o Oxygen until hypoxemia corrected – first by FiO2, then CPAP/BiPAP, then intubate o If below meds don’t work – intraaortic balloon pump o Medications  Lasix (Loop diuretic)*  Natriuretic Peptides  Nitroglycerin*  Inotropes  Pressors  * indicates contraindicated if hypotensive. NB that the goal of treatment is to reduce preload, pulmonary edema, wall stress, increase CO, and maintain BP

Question 31

Tx of chronic HF

Answer 31

Investigations – Bloodwork, ECG, CXR, Echo Management o Exercise training o Salt/fluid restriction o Weight management o Medications  ACEi (Reduce preload and afterload)  Beta-blockers (Reduce cardiac workload)  ARB (Reduce preload and afterload)  Digoxin (Inotrope, negative chronotrope, anti-arrhythmic)  Nitrates (Reduce preload and some afterload)  Spironolactone (Aldosterone blocker) (Reduce preload) ``` o Procedures  Cardiac Resynchronization Therapy  ICD  Revascularization if indicated  Cardiac transplant ```

Question 32

Benefits of cardiac rehab (exercise)

Answer 32

Reduced HR and systolic BP to submaximal heart workload Increase peak coronary flow Improvement in CV and pulmonary function Reduction in CAD risk factors Changes in systemic circulation during exercise - increase in systolic BP, decrease SVR, decrease diastolic BP

Question 33

Risks of exercise

Answer 33

Reduce "rate pressure product" = HR x SBP Acutely increase risk of a medical event - vigorous exercise (increase SNS, decrease vagal, increase max VO2) --> ischemia

Question 34

VO2 max

Answer 34

The maximum about of O2 taken in, transported and used while performing at peak intensity Fick Equation: VO2= (HRmax × SVmax) × (CaO¬2max × CvO¬2max) CaO2 = arterial oxygen content CvO2 = venous oxygen content

Question 35

Lactic threshold

Answer 35

lactate production > metabolism (>40% max VO2 in normal individuals)

Question 36

Metabolic equivalents

Answer 36

standard unit to measure oxygen usage during exercise 1 MET = O2 used at rest (3.5 ml O2/kg/min) 3-6 METs - moderate intensity >6 - vigorous

Question 37

Inotrope and pressor types

Answer 37

Dopamine, dobutamine, epi, norepi

Question 38

Inotrope/pressor MOA and indication

Answer 38

beta adrenergic --> increase Ca availability --> increase contractility --> increase SV/CO alpha --> increase peripheral v/c Norepi: more on alpha 1 Epi: more on beta 1 and 2 Indications: more useful for patient with systolic ventricular dysfunction - iv, temporary hemodynamic support for acutely ill, hospitalized patients

Question 39

Morphine (CHF) MOA and indiactions

Answer 39

release of vasoactive histamine --> peripheral v/d Sympatholytic (central) Reduce systemic catecholamines --> decrease HR, BP, contractility Effect: decrease preload (improve pulmonary congestion), decrease O2 demand, agitation, sense of SOB Indicated in: acute CHF + pulmonary congestion

Question 40

Diuretic use in HF

Answer 40

Pulmonary congestion (rales) or edema ``` Adverse effects: vigorous diuresis --> decrease in CO electrolyte disturbances (hypokalemia) --> arrhythmia Patients with LV diastolic dysfunction, be careful with overdiuresis (need high preload to sustain function) ```

Question 41

Nitrate use in HF

Answer 41

acute and chronic HF improve pulmonary congestion same adverse effect as diuretics

Question 42

ACEi in HF

Answer 42

Chronic CHF only reduce pulmonary congestion, remodelling, reduce HF symptoms CI: pregnancy, renal dysfunction adverse effect: dry cough, hyperkalemia, hypotension, renal dysfunction, angioedema

Question 43

ARB for HF

Answer 43

chronic HF Indiations: 2nd line after ACEi CI: pregnancy

Question 44

b-blocker for HF

Answer 44

Chronic CHF Effect: paradoxically improve CO - reduce hemodynamic deterioration, improve survival CI: ACUTE HF, asthma

Question 45

Medical management of acute HF

Answer 45

diuretic, morphine, NTG, inotropes NOT b-blockers, ACEi

Question 46

Medical management of chronic HF

Answer 46

ACEi, b-blocker, diuretic, digoxin

Question 47

ACC/AHA classification of HF

Answer 47

A. At risk for heart failure but without structural heart disease or symptoms B. Structural heart disease but without heart failure C. Structural heart disease with prior or current heart failure symptoms D. Refractory heart failure requiring specialized interventions

Question 48

NYHA classification of HF

Answer 48

I. Asymptomatic HF: no symptoms II. Mild HF: symptomatic with moderate exertion III. Moderate HF: symptomatic with minimal exertion IV: Severe HF: symptomatic at rest