HEART FAILURE PART 1:PATHOPHYSIOLOGY

DISCLOSURE

Relevant relationships with commercial entities – none

Potential for conflicts of interest within this presentation – none

Steps taken to review and mitigate potential bias – N/A

LEARNING OBJECTIVE

This lecture is designed to meet the following end‐of‐week learning objective:1. Define heart failure, ventricular remodelling, 

systolic dysfunction and diastolic dysfunction2. Describe neurohormonal changes in heart 

failure3. List common causes of heart failure

MODULE OBJECTIVES

By the end of this module, you should be able to:1. Define heart failure as a pathologic syndrome2. List some common causes of heart failure3. Describe the pathophysiology of the heart failure 

state including:– Myocardial injury and remodelling– Concentric versus eccentric remodelling– Systolic and diastolic dysfunction

WHAT IS HEART FAILURE (HF)?

“HF is a complex syndrome in which abnormal heart function results in, or increases the subsequent risk of, clinical symptoms and signs of low cardiac output and/or pulmonary or systemic congestion”

The heart as a pump is too weak or too stiff to maintain circulation without running the risk of congestion

CAUSES OF HEART FAILURE:UNDERLYING STRUCTURAL HEART 

DISEASESHF can result from any form of heart disease 

A useful approach is to classify causes anatomically:

• Coronary arteries MI, chronic ischemic heart disease

• Myocardium Cardiomyopathies, with or without identifiable known cause

• Endocardium Valvular disease

• Pericardium Constrictive pericarditis

• Systemic diseases Anemia, nutritional, metabolic

Abnormal anatomy: Myocardial Infarction

Abnormal histology: Acute Phase of a Myocardial

Infarction

PATHOPHYSIOLOGY ‐ SCHEME

Normal Heart

Function

INJURY(ischemia/infarct, inflammation, etc.)

Early Dysfunction

NeurohormonalActivation

PersistentDysfunction

Normal Heart

FunctionImplies transientand reversible insult (rare?)

Myocyte death, fibrosis, remodelling

PersistentDysfunction Symptoms

Compensatedphase

Decompensatedphase

Refractory HF,Death,

Transplantation

medical, device and surgical therapy

PATHOPHYSIOLOGY ‐ SCHEME

Stage AHigh risk,

no symptoms

Stage BStructural disease

No symptoms

Stage CSymptomatic

Stage DRefractory symptoms

Very advanced HF

Disease Trajectory

SPECTRUM OF HF

BACK TO PHYSIOLOGY:FRANK‐STARLING CURVE

FRANK‐STARLING CURVE & LEFT VENTRICULAR DYSFUNCTION

FRANK‐STARLING CURVE & LEFT VENTRICULAR DYSFUNCTION

INCREASED VOLUME AND PRELOAD: DIFFICULT BALANCE

Elevated Filling

Pressures

“Back-pressure”transmitted

Obligatory rise in driving pressure

LEFT VENTRICULAR FAILURE

NEUROHUMORAL ACTIVATION when the heart begins to fail

C.O. and systemic blood pressure

Activation of Renin-angiotensin

Aldosterone system

Non-osmoticrelease of

vasopressin

Activation of Sympathetic

Nervous system

Augmented HR, contractility vasoconstriction, decreased renal

excretion of Na/H20

Restoration of circulating

volume/preload andC.O.

CONCEPT OF REMODELLING• Anatomic changes in the ventricle that are initially adaptive to hemodynamic stress following myocardial injury

• Altered geometry and cell biology of the myocardium later becomes maladaptive as it is mechanically disadvantageous

• Neurohumoral activation is the key underlying mechanism

Normal Eccentric hypertrophyi.e., volume overload

For a given ejection fraction,stroke volume is greater with eccentric hypertrophy

REMODELLING CAN RESULT IN ECCENTRIC HYPERTROPHY

EXAMPLE: DILATED CARDIOMYOPATHY

REMODELLING CAN RESULT IN CONCENTRIC HYPERTROPHY

Normal LV Hypertrophy (i.e., pressure load)

Laplace’s Law: Wall Tension ~ Pressure x radiush

r r

h (thickness) h (thickness)

EXAMPLE:HYPERTENSIVE CARDIOMYOPATHY

ANOTHER EXAMPLE:HYPERTROPHIC CARDIOMYOPATHY

Neurohumoral activation is a central mechanism of progressive HF

LV dysfunction

NeurohormonalActivation

Progressive LV Remodeling

Myocardial insult

• Initially supports the circulation – enhanced Na/H2O retention, vasoconstriction

• Ultimately highly negative impact - myocyte necrosis, progressive remodelling

• A principle target for medical therapy

SO….

Following injury, the LV can “compensate” and maintain adequate circulation

Occurs at the expense of:– Unfavorable geometric changes– Increased circulating catecholamines, AT II, etc.

SYSTOLIC VS. DIASTOLIC LV DYSFUNCTION

Normal LV

Impaired filling“diastolic HF”

Impaired contraction“systolic HF”

• Preserved systolic function• Normal LV size• Concentric hypertrophy• Increased wall thickness

• Low LV ejection fraction

• LV dilatation• Eccentric hypertrophy• Normal wall thickness

May coexist

Systolic Dysfunction

Normal

LOWER TOTAL STROKE VOLUME IN SYSTOLIC DYSFUNCTION

Diastolic Dysfunction

Normal

LOWER TOTAL STROKE VOLUME IN DIASTOLIC DYSFUNCTION

REVIEW

By now, you should be able to:1. Define heart failure as a pathologic syndrome2. List some common causes of heart failure3. Describe the pathophysiology of the heart failure 

state including:– Myocardial injury and remodelling– Concentric versus eccentric remodelling– Systolic and diastolic dysfunction