PATHOPHYSIOLOGY OF HEART FAILURE - …c.ymcdn.com/sites/ OF HEART FAILURE Sara ... due to decreased cardiac output with heart failure NEW HYPOTHESIS: Renal dysfunction in patients
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5. Pulmonary hypertension with unclear multifactorial
mechanisms
Simonneau et al. Updated Clinical Classification of Pulmonary Hypertension. JACC 2009, 54(1); S43-S54.
2. Pulmonary hypertension due to
left heart disease• Pulmonary venous hypertension
• Systolic dysfunction
• Diastolic dysfunction
• Valvular disease
• The most common
cause of pulmonary
hypertension
Pulmonary
Artery
Pulmonary
Veins
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Now let’s bring the kidneys into the
picture…..
How are the kidneys affected in
heart failure???
Traditional Assumption:
Renal dysfunction is secondary to renal hypoperfusion
due to decreased cardiac output with heart failure
NEW HYPOTHESIS:
Renal dysfunction in patients with heart failure is more
strongly associated with venous congestion than with
reduced cardiac output
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Cardiorenal syndrome
Arterial blood flow
Venous blood flow
> 0.3 mg or 25% increase in creatinine
Hemodynamic Changes
Pathophysiology: Symptoms vs
Disease Progression
What produces progression?
Neurohormonal abnormalities
• Activation of renin-angiotensin system (RAS) andsympathetic nervous system (SNS)
• Cytokines, endothelin, vasopressin, others, etc.
What produces symptoms?
Hemodynamic abnormalities
— Changes in cardiac function and peripheral hemodynamics
Cohn JN. N Engl J Med. 1996;335:490–498.
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Cardiac Performance• Preload
• End diastolic ventricular stretch (pressure)
• Determined by venous return (ventricular filling)
• Afterload
• Arterial pressure the ventricle must pump against; aortic
pressure for LV, pulmonary pressure for RV
• Increased by norepi, angiotensin II, vasopressin
Frank-Starling Curve
2-7 mmHg
25/9 mmHg
10mmHg
25/9 (14)
90-140/5-12
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Pulmonary Hypertension or Left Heart Failure
Right Heart
Failure
Venous
CongestionWorsening
Renal Function
Right heart failure: mitral stenosis
Valve stenosis
affecting right heart muscle
Some terminology:
LV Ejection Fraction• The percentage of blood volume ejected from the left
ventricle with each heartbeat.
• Normal = 60%
• Is a measurement of the strength of contraction
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2 Types of heart failure
Filling Dysfunction (HFpEF)
• Heart failure symptoms with EF 40%
• Hypertrophic CMP, HTN, Ischemia, Age
• Impaired relaxation
Contractile Dysfunction (HFrEF)
• Depressed contractility EF 40%
• CAD, Valve disease, Ischemic and Idiopathic
CMP
• Impaired contractility
Definition of Heart FailureClassification Ejection
Fraction
Description
I. Heart Failure with
Reduced Ejection Fraction
(HFrEF)
≤40% Also referred to as systolic HF. Randomized clinical trials have
mainly enrolled patients with HFrEF and it is only in these patients
that efficacious therapies have been demonstrated to date.
II. Heart Failure with
Preserved Ejection
Fraction (HFpEF)
≥50% Also referred to as diastolic HF. Several different criteria have been
used to further define HFpEF. The diagnosis of HFpEF is
challenging because it is largely one of excluding other potential
noncardiac causes of symptoms suggestive of HF. To date,
efficacious therapies have not been identified.
a. HFpEF, Borderline 41% to 49% These patients fall into a borderline or intermediate group. Their
characteristics, treatment patterns, and outcomes appear similar to
those of patient with HFpEF.
b. HFpEF, Improved >40% It has been recognized that a subset of patients with HFpEF
previously had HFrEF. These patients with improvement or recovery
in EF may be clinically distinct from those with persistently
preserved or reduced EF. Further research is needed to better
characterize these patients.
HFrEF HFpEF
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Symptom Development
Symptoms are the “Tip of the Iceberg”
in Heart Failure
Dyspnea
FatigueEdema
Orthopnea
Neurohormonal
Activation
Volume
Overload
Pressure
Overload
LV Remodeling
Fibrosis
Cytokines
Vasoconstriction
Index Event
Left Ventricular Remodeling
Neurohormonal Activation
Reduced Myocardial Function
Volume Overload & Elevated LV Filling Pressure
SymptomsDyspnea
Fatigue
Edema
Orthopnea/PND
Cough
Water is pushed out into interstitial space
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Definition of Heart Failure:
Old and New
Old definition
State in which the heart is unable to pump enough blood to meet the metabolic demands of the body
New definition
Complex clinical syndrome that results from structural and functional changes in the heart that all occur in the milieu of neurohormonal activationand cytokine release
A clinical syndrome or condition rather than a disease; the end result of a variety of diseases.