SICU Meeting

Diastolic Dysfunction

日期： 2003.05.05
報告者： Ri 張家豪
Overview
 CHF resulting from the abnormalities of
systolic function is well recognized
 Diastolic dysfunction is increasing recognized
as an important cause of heart failure
 About 1/3 of heart failure is predominantly
diastolic, 1/3 is systolic, 1/3 is combined
 Prevalence of diastolic dysfunction varied
from 13% to 74% Vasan R.S. et al. Prevalence, clinical features and
prognosis of diastolic heart failure: epidemiologic perspective. J Am Coll Cardiol
1995;26:1565-74
Definition
 Diastole: the time period during which
myocardium loses ability to generate force
and shorten and returns to an unstressed
length and force
 Diastolic dysfunction: prolonged, slowed, or
incomplete of diastole process
 Diastolic heart failure: a clinical syndrome
characterized by the s/s of heart failure, a
preserved EF and abnormal diastolic function
Physiology of contraction & relaxation
Systole and diastole phases
Pathophysiology
 Impaired relaxation
‧Ischemia results in upward shift of LV pressure-volume
relationship
‧Sarcoplasmic reticulum Ca2+ ATP-ase pump (SERCA):
remove Ca2+ from the cytosol
‧Phospholamban: SERCA-inhibitory protein; impair
relaxation
‧LVH, hypertrophic or dilated cardiomyopathy,
hypothyroidism →decreased SERCA, increased
phospholamban
‧Levels of SERCA decrease with age

Circulation. 2003;107:659-663
Pathophysiology
 Increased passive stiffness
‧Fibrillar collagen play an important role in the
development of diastolic dysfunction
‧Collagen synthesis is altered by load, neurohormonal
activaion (RAAS), sympathetic nervous system, and GF
‧Stiffness increased in patients with focal scar or
aneurysm after MI, myocyte hypertrophy, or infiltrative
cardiomyopathies
Circulation. 2003;107:659-663
Circulation. 2002;105:1503-1508
Factors Increasing Diastolic Pressure

Impaired Ventricular Relaxation Increased Ventricular Stiffness

Hypertrophy Hypertrophy
Myocardial ischemia Hypertension
Hypertension Collagen deposition and fibrosis
Collagen deposition and fibrosis Cellular disarray
Regional asynchrony Myocardial infiltration
Increased preload, afterload Pericardial constriction or restriction
Abnormal calcium flux
Tachycardia
Causes of Isolated Diastolic Dysfunction

Common Less Common

Coronary artery disease Hypertrophic

Hypertension cardiomyopathy
Aging Infiltrative cardiomyopathies
Diabetes mellitus Endocardial fibroelastosis
Obesity Pericardial disease
Aortic stenosis
Hypertensive Heart Disease
 Impaired sarcoplasmic reticulum function and
resultant Ca2+ overload
 Compliance reduced due to↑wall thickness,
myocardial fibrosis and collagen deposition
 Neurohormonal influence (RAAS)

Harrison 15th edition; Chapter 231

Coronary Artery Disease
 Ventricular relaxation is an energy-dependent
process
 Diastolic dysfunction precedes development
of regional wall motion abnormalities
 Chronic ischemia can result in myocardial
scarring and fibrosis and reduced compliance

Harrison 15th edition; Chapter 231

Hypertrophic Cardiomyopathy

 Idiopathic ventricular hypertrophy is

characterized by impaired diastolic function
 Increased chamber stiffness and abnormal
relaxation can be seen

Harrison 15th edition; Chapter 231

Restrictive Cardiomyopathy
 RCM is defined as a disease of the myocardium in which
there is markedly increased stiffness of either the
myocardium or endocardium
 Primary form: endomyocardial fibrosis, Loeffler’s syndrome,
and idiopathic RCM
 Secondary form: infiltrative disorders (amyloidosis,
sarcoidosis, metastatic malignancies…) and storage
disorders (hemochromatosis, glycogen storage disease,
and Fabry’s diasease)
Harrison 15th edition; Chapter 231
Constrictive Pericarditis
 A rigid encasement of the heart by thickening and
fibrosis of the pericardium
 Idiopathic, viral, bacterial, fungal, and tuberculous
pericarditis can all result in late constriction
 Post-infarction and post-pericardiotomy can lead to
chronic constriction
 Mediastinal radiotherapy-usually 5-10 years after
therapy
Harrison 15th edition; Chapter 231
Diagnosis
 Diagnosis of DHF cannot be made at the
bedside
 Differentiation between systolic and diastolic
cannot be made based on history, PE, ECG
or CXR
 Many criteria, lots of controversy
Principles of diagnosis
 Establish clinical diagnosis of congestive heart
failure
 Confirm normal systolic function
 Document elevated left ventricular end-diastolic
pressure
 Perform echocardiographic studies to detect
evidence of abnormal diastolic function
Framingham criteria for CHF
MAJOR CRITERIA MINOR CRITERIA

Paroxysmal nocturnal dyspnea Extremity edema

Neck vein distention Night cough
Rales Dyspnea on exertion
Cardiomegaly Hepatomegaly
Acute pulmonary edema Pleural effusion
S3 gallop Vital capacity reduced by one-third from
Increased venous pressure (>16 cmH2O) normal
Positive hepatojugular reflux Tachycardia (≥120 bpm)

MAJOR OR MINOR

Weight loss ≥4.5 kg over 5 days'

treatment
To establish a clinical diagnosis of congestive heart failure by these criteria, at least one major
and two minor criteria are required.

KKL Ho et al, Circulation 88:107, 1993.

Symptoms and signs: systolic vs diastolic
Symptoms and signs: systolic vs diastolic

Circulation. 2002;105:1387-1393
European Study Group on DHF
 Presence of s/s of CHF
 Presence of normal or only mildly abnormal LV
systolic function (normal LVEF: >45%)
 Evidence of abnormal LV relaxation, filling,
diastolic distensibility or diastolic stiffness

European Study Group on Diastolic Heart Failure. How to diagnose siastolic heart
failure.

Eur Heart J. 1998;19:990-1003

Vasan and Levy
 Definite:
‧Definitive evidence of CHF
‧Objective evidence of normal systolic function, EF>50% within 72
hours of the CHF event
‧Objective evidence of diastolic dysfunction on catheterization
 Probable:
‧ Objective diastolic dysfunction is lacking
‧ First 2 criteria are present
 Possible:
‧ First criterion is present
‧ EF>50% but not assessed within 72 hours

Vasan RS, Levy D. Defining diastolic heart failure: a call for standardized diagnostic criteria.
Circulation. 2000; 101:2118-2121
Measurement of Diastolic Function
 Can be divided into those that reflect the process
of active relaxation and those that reflect passive
stiffness
 Structures and processes that alter relaxation
can also result in measurable abnormalities in
stiffness
 However, it’s necessary to develop methods of
measurement
Measurement of Active Relaxation
 IVRT: isovolumic relaxation time
 Transmitter Doppler LV inflow velocity;
Pulmonary vein Doppler velocity; Doppler tissue
velocity
 E-wave: early LV filling velocity
 A-wave: velocity of LV filling contributed by atrial
contraction
 Deceleration time: E-wave deceleration time
Systole and diastole phases
Doppler-Identified Stages of Diastolic
dysfunction
 Impaired Relaxation
E/A ratio <1 or DT >240 ms in patients <55 y/o
E/A ratio <0.8 and DT >240 ms in patients> 55 years of age
 Pseudonormal
E/A ratio of 1 to 1.5 and DT >240 ms.
PVd/PVs >1.5 or IVRT <90 ms or by reversal of the E/A ratio (to
<1.0) by Valsalva when possible.
 Restrictive like
DT <160 ms with 1 of the following:
left atrial size >5 cm
E/A >1.5
IVRT <70 ms
PVd/PVs >1.5
Stages of Diastolic dysfunction
Measurement of Stiffness
 Changes in myocardial stiffness can be assessed
by examination of the the pressure and volume
relationship
 Stiffness at any point is equal to the slope of a
tangent drawn to the curve at that point (dP/dV)
Pressure-Volume of Diastolic
dysfunction
Pressure-volume relationship
B-type Natriuretic Peptide (BNP)
 A cardiac neurohormone, was first discovered in the brain
of pigs
 32 amino acid polypeptide containing a 17 amino acid
ring structure
 Regulate blood pressure and fluid balance by counter
balancing the renin-angiotensin system
 In humans, the main source of BNP is the ventricles of
the heart
 Circulating BNP levels increase in proportion to the
severity of the disorder, and is detectable with minimal
clinical symptoms
B-type Natriuretic Peptide (BNP)
 An independent, significant predictor of high left
ventricular end-diastolic pressure in patients with CHF.
 A tool to distinguish CHF from other cause of acute
dyspnea
 Serial BNP measurement can predict outcomes in
patients hospitalized for decompensated heart failure
 The simplest definition of DHF may be an elevated BNP
with normal systolic function
B-type Natriuretic Peptide (BNP)

Maisel A. S., et al, from the Division of Cardiology and Department of Medicine, Veteran’s Affairs Medical Center and
University of California, San Diego: Utility of B-natriuretic peptide as a rapid, point-of-care test for screening patients
undergoing echocardiography to determine left ventricular dysfunction. August 2000.
B-type Natriuretic Peptide (BNP)

Maisel A. S., et al, from the Division of Cardiology and Department of Medicine, Veteran’s Affairs Medical Center and
University of California, San Diego: Utility of B-natriuretic peptide as a rapid, point-of-care test for screening patients
undergoing echocardiography to determine left ventricular dysfunction. August 2000.
Prognosis
 Mortality:
‧Annual mortality rate for DHF: 5% to 8%
‧SHF: 10% to 15%
‧>70 y/o, mortality rate for SHF and DHF are nearly equivalent
‧Prognosis is affected by the pathological origin
‧Other determinants include age, EF cutoff and study design
 Morbidity:
‧Quite high in frequent outpatient visit, hospitalization, and
expenditure of healthcare
‧1-year readmission rate approaches 50%
‧Morbidity rate is nearly identical to that SHF
Circulation. 2002;105:1387-1393
DHF: Effects of Age on Prevalence and
Prognosis

Circulation. 2002;105:1387-1393
Circulation. 2002;105:1503-1508
Randomized Clinical Trials for DHF

Circulation. 2002;105:1387-1393
Summary
 DHF is not at all rare and may account for a large
number of the hospitalization
 Clinical and echocardiographic criteria are still
imperfect
 Incorporation of BNP measurement may increase the
accuracy of diagnosis
 Further evidence of treatment should be available
from randomized therapeutic trials

Circulation. 2003;107:659-
663