the clinical syndrome of heart failure
TRANSCRIPT
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Brian Jensen MDUNC Mini Medical School
February 3, 2020
The Clinical Syndrome of Heart Failure
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Case PresentationHPI: 57 year-old man with a history of myocardial infarction in 2016 presents with worsening shortness of breath for the past two weeks. He was able to walk around WalMart three times prior to Thanksgiving, but now becomes short of breath walking around his house. He also reports leg swelling to his knees, abdominal bloating, and a 20 lb weight gain. He has had difficulty sleeping as he becomes short of breath when he lies down. As a result he has been sleeping on 3 pillows and occasionally has to sit up on the edge of the bed to catch his breath. These are all new symptoms for him.
Physical Exam: mildly tachypneic with prolonged conversationHR 105 bpm BP 98/74 mmHg O2 88% on RA, 95% on 2L NJVP 14-16 cm H2OBibasilar ralesTachycardic S1S2 +S3 and 2/6 holosystolic murmur at the apexDistended, non-tender, liver edge 3cm below costal marginLE slightly cool to touch, 2+ pitting edema to mid thigh
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Definition (Practical)
Heart FailureA complex clinical syndrome that results from
maladaptive neurohormonal responses to decreased cardiac performance and is most commonly characterized by fluid retention
and effort intolerance
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Heart Failure StatisticsThe obligatory burden of disease slide…
AHA Statistical Update
6 million people have HF ~700,000 new cases annually
~300,000 annual deaths due to HF 1.1 million hospitalizations per year
Largest Medicare expenditure…$35-40 billion yearly
Prevalence increases with age
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Causes of Heart FailureHeart Failure as a final common pathway
Heart Failure
Myocardial Infarction
ValvularDisease
Hypertension
Congenital Heart Disease
Cardiomyopathy
Arrhythmia
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Eje
ctio
n F
ract
ion
(C
on
trac
tile
Fu
nct
ion
) 60 %
20 %Time (months to years)
Compensatory Mechanisms
(and medications)
SecondaryDamage
(maladaptiveneurohormonal
responses)
Asymptomatic Symptomatic
Mann, Circulation 1999; 100: 999-1008
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Heart failure is progressive and has a poor prognosis
Mean survival after diagnosis of heart failure is 5 yearsMean survival after first hospitalization for acute decompensated HF (ADHF) = 2.4 years
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Causes of Heart FailureIschemic “Cardiomyopathy”
EARLY: Neutrophilic infiltrate, necrosis, hemorrhage
LATE: Extensive fibrosis
Myocardial infarction (“ischemic cardiomyopathy”) is the most common cause of HF.The problem with the muscle is secondary to a problem in the coronary arteries
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Causes of Heart FailureMyocardial Infarction: Dead Meat Don’t Beat
Coronary Angiogram
Coronary artery with plaque rupture
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Yeah, but what is heart failure?The Hemodynamic or “Mechanical” Paradigm
=1
4
6
https://www.clevelandclinic.org/heartcenter/images/guide/heartworks/heart_bloodvessels.jpg
The heart is a pump. The blood vessels are pipes that enter and leave the pump.
Heart failure is pump failure…
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Diagnosis of heart failureEchocardiogram (cardiac ultrasound)
Normal Heart Failure Systole = contractionDiastole = relaxation
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Blood pressure
Regulation of blood pressure is the central function of the cardiovascular system
Cardiac Output
(CO)
Systemic Vascular
Resistance (SVR)
Heart Rate (HR)
Stroke Volume
(SV)When contractility decreases
after injury, the body will respond by retaining fluid to
expand blood volume to increase stroke volume.
Contractility
Ohm’s LawV = IR
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Neurohormonal ParadigmA series of Maladaptive Responses
http://www.cvphysiology.com/Blood%20Pressure/BP015.htm
NorepinephrineHeart Failure is not just a disease of the heart!
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Sympathetic nervous system activation“Fight or flight” with epinephrine and norepinephrine
1-AR1-AR
1-ARNE
NENE
1-AR stimulation by norepinephrine increases heart rate (chronotropy) and
contractility (inotropy)
Acutely, these changes are adaptive and can improve cardiac output in a heart with impaired contractility
NEIncreased renin releaseIncrease fluid retention (preload)
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Maladaptive chronic sympathetic surgeAll this fighting or fleeing is tough on the heart
Norepinephrine and EpinephrineGreat for acute responses, but toxic with sustained exposure
Cardiovascular response to chronic -AR stimulation
Downregulation of 1-ARs
Unfavorable changes in 1-AR signaling
Energy starvation
Cardiomyocyte death
Ventricular arrhythmias
Fibrosis
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Sympathetic Activation in Heart FailureCatecholamines are elevated in HF and contribute to its progression
Disease progression
Cardiac sympatheticactivity
-adrenergicreceptors
VasoconstrictionSodium retention
Myocardial toxicityIncreased arrhythmias
Renal and vascularsympathetic activity
Activationof RAAS
-AR
Adapted from Packer M. Progr Cardiovasc Dis. 1998;39(Supp I):39-52
a1-AR
Perfusion causes
CNS sympathetic outflow
EpinephrineNorepinephrine
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Renin-Angiotensin-Aldosterone System (RAAS)The response to decreased stroke volume
The kidneys sense decreased effective arterial blood volume and increase renin release from the juxtaglomerular apparatus, leading to increased angiotensin II
and aldosterone levels -> increased blood volume and vasoconstriction.
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Renin-Angiotensin SystemPromotes retention of sodium/water and vasoconstriction
http://en.wikipedia.org/wiki/File:Renin-angiotensin-aldosterone_system.png
Heart Failure disrupts this negative feedback loop. Decreased cardiac output decreases renal perfusion…
…and thus creates a positive feedback loop …
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Fluid retention increases pressure in the heart, which causes edema
https://www.clevelandclinic.org/heartcenter/images/guide/heartworks/heart_bloodvessels.jpg
Alveolus
Pulmonary Capillary
High LVEDP = high left atrial pressure
High pulmonary vein pressure
High pulmonary capillary pressure
Many of the symptoms of heart failure, regardless of cause, result from
increased left atrial pressure
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Left Heart Failure Pulmonary Edema
Pulmonary edema
Markedly elevated preload can cause pulmonary edema (fluid in the lungs), contributing to dyspnea (most common symptom of HF)
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Right Heart Failure = increased RA pressureIncreased right ventricular preload communicated to systemic veins
1
4
6
https://www.clevelandclinic.org/heartcenter/images/guide/heartworks/heart_bloodvessels.jpg
JVD
Lower Extremity Edema
HepatomegalyAscites
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Neurohormonal responses underlie heart failureHeart failure results from maladaptive feedback loops
Myocardial Insult
Myocardial Dysfunction
Renin-Angiotensin-Aldosterone (RAA)
System ActivationSympathetic System
Activation
Altered Gene ApoptosisExpression
Remodeling
Reduced System Perfusion
These processes drive the transition from injury to heart failure
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Neurohormonal Paradigm RevisitedTargets for Evidence-Based Therapy
Renin
Angiotensin I
Aldosterone
Norepinephrine
Other players: Endothelin, Vasopressin, ANP, BNP, etc
chronotropy, inotropy, vasoconstriction, reninsecretion
sodium retention, cardiac fibrosis
Angiotensin II
vasoconstriction, cardiomyocyte hypertrophy, aldosterone and vasopressin release, thirst
Converts angiotensinogen to angiotensin I
✖Angiotensin
Receptor Blockers (ARBs)
✖ACE inhibitors
✖AldosteroneAntagonists
✖-blockers
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MERIT-HF Study Group. LANCET. 1999;353:2001-2007.
12%
24%64%
NYHA Class II
26%
15%59%
NYHA Class III
56%
11%
33%Heart
Failure
Other
NYHA Class IV
What Kills Heart Failure Patients?Sudden Cardiac Death (SCD)/Arrhythmia
Sudden Death
5-year mortality following HF diagnosis
= 45-60%
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Implantable Cardioverter DefibrillatorsICDs
Axillary or Subclavian Vein
Right Ventricular apex
Right atrium
ICD
Senses life-threatening rhythms and electrically terminates them
Serves as a pacemaker for slow rhythms
All abnormal rhythms are recorded
2006-2009 ICD Registry:486,000 implants in US141,000 implants in 2009
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ICDs prevent SCD in Heart FailureMADIT-II (primary prevention)
Moss AJ. N Engl J Med. 2002;346:877-83.
HR mortality = 0.69
p = 0.007
1.0
0.9
0.8
0.7
0.6
0
Pro
bab
ility
of
Surv
ival
Defibrillator
Conventional
0 1 2 3 4
Year
Ejection Fraction (EF) < 30%NYHA Class I-III
No prior life-threatening arrhythmias
N.B. Normal Ejection Fraction (EF) > 55%
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• Long ventricular conduction time causes dyssynchrony and inefficient contraction
• QRS > 120 msec required to derive benefit
• Pacing the interventricular septum (“RV lead”) and LV free wall resynchronizes contraction
• Improved pumping efficiency results from resynchronization
Cardiac Resynchronization Therapy (CRT) Implantation of a Biventricular Pacemaker
Sinus node
AVnode
Stimulation by pacemakerleads
Conduction block
Wide QRS
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CRT decreases all-cause mortalityCARE-HF Trial
0 500 1000 15000.00
0.25
0.50
0.75
1.00
Eve
nt-
fre
e S
urv
ival
Days
Medical Therapy
HR Mortality = 0.64 p = .0019
CRT
n = 813 with NYHA III (94%) or IV HF; EF < 35%QRS >150ms or QRS 120-149 ms (with dyssynchrony)
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Heart transplant is the only cure for heart failure
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
Surv
ival
(%
)
Years
Cardiomyopathy (N=44,736) CAD (N=40,272)
Congenital (N=1,983) Retransplant (N=1,997)
Valvular (N=3,469)
Median survival (years): Cardiomyopathy= 11.8; CAD=9.5; Congenital=14.7;
Retransplant=6.6; Valvular=11.0
2014
JHLT. 2014 Oct; 33(10): 996-1008
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US Dept of HHS Scientific Registry of Transplant Recipientssrtr.transplant.hrsa.gov
Organ (donor) shortageRoughly 50% of wait-listed patients are transplanted yearly
Percentage undergoing transplantDonation rates are stable at roughly 4 per 1000 deaths
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Left Ventricular Assist DevicesBridge to Transplant (or “Destination Therapy”)
Flow is directed from the apex of the left ventricle to the ascending aorta
Controller
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