Transcript ΚΑΡΔΙΑΓΓΕΙΑΚΗ ΝΟΣΟΣ ΗΛΙΚΙΩΜΕΝΩΝ

ΚΑΡΔΙΑΓΓΕΙΑΚΗ ΝΟΣΟΣ
ΣΤΟΥΣ ΗΛΙΚΙΩΜΕΝΟΥΣ
ΑΝΔΡΕΑΣ ΠΙΤΤΑΡΑΣ MD
“ Seventy is old enough.
After that there is too much risk.”
Mark Twain
Following the Equator, 1897
Introduction
• Cardiovascular disease (CVD) is the
leading cause of death in the elderly.
• 5 out of every 6 deaths related to CVD
occur in the elderly.
• Nearly 2/3 of all myocardial infarctions and
80% of all deaths related to MI occur in
persons over 65 years of age.
Cardiovascular disease in the elderly
• Coronary artery disease
• Heart failure
• Valvular heart disease
• Atrial fibrillation
Cardiovascular Health Study
• Population-based study of risk factors for
cardiovascular disease in older patients.
• Participants > 65 were recruited from
random samples of Medicare eligibility lists
in four communities (CA, MD, NC and PA)
• Presence of CVD was not an exclusion.
J Am Geriatric Soc 2005; 53: 211-218
Cardiovascular Health Study
• Original cohort ( n = 5201) enrolled in
1989-1990
• 2nd cohort ( n = 687) of predominately AA
enrolled 3 years later to increase diversity
• Combined cohort of 5,888 patients was
57.6% female and 15.7% African American
• Average age at entry was 72.8 years +/- 5.6
Coronary artery disease
Cardiovascular Health Study
10 yr incidence rates: CHD in women
40
35
30
25
65-69
70-74
75-79
80-84
20
15
10
5
0
Caucasian
African American
Cardiovascular Health Study
10 yr incidence rates: CHD in men
70
60
50
65-69
70-74
75-79
80-84
40
30
20
10
0
Caucasian
African American
Coronary artery disease in the elderly
• Coronary heart disease (CHD) may often
present atypically in the elderly.
• Dyspnea or acute heart failure may be the
initial manifestation of myocardial ischemia
or infarction.
• CHD is often undiagnosed or misdiagnosed
in elderly patients.
Acute coronary syndrome:
Differences by age
• 2133 consecutive acute coronary syndrome
(ACS) patients from 26 hospitals
participating in a nationwide survey
• Three patient subgroups based on age:
< 65 years
65 - 75 years
> 75 years
(n = 974)
(n = 500)
(n = 639)
Am J Geriatric Cardiol 2004; 13: 188-196
Baseline characteristics of
ACS patients: Differences by age
60
50
40
< 65
65-75
> 75
30
20
10
0
h/o angina
h/o MI
h/o CHF
Initial symptoms & ECG findings in
ACS patients: Differences by age
90
80
70
60
< 65
65-75
> 75
50
40
30
20
10
0
angina
ST elevation
ST depression
In-hospital complications in
ACS patients: Differences by age
30
25
20
< 65
65-75
> 75
15
10
5
0
CHF
New BBB
PAF
In-hospital mortality in
ACS patients: Differences by age
35
30
25
20
< 65
65-75
> 75
15
10
5
0
7 days
30 days
1 year
In-hospital management in
ACS patients: Differences by age
70
60
50
40
< 65
65-75
> 75
30
20
10
0
angiography
stenting
CABG
Global Registry of
Acute Coronary Events (GRACE)
• Observational registry of patients admitted
to hospital with acute coronary syndrome
• 24,165 ACS patients (2/3 men) stratified
into 4 age groups
• 102 participating hospitals in 14 countries
Am Heart J 2005; 149: 67-73
Global Registry of
Acute Coronary Events (GRACE)
• Patients > 65 more commonly had a past
medical history of:
angina
previous MI
CABG
atrial fibrillation
TIA/stroke
heart failure
hypertension
Global Registry of
Acute Coronary Events (GRACE)
• Older patients demonstrated a higher
incidence of non ST-segment elevation MI
(NSTEMI)
• Patients > 65 exhibited a significant delay in
seeking treatment
Comparison among age groups
according to type of ACS
45
40
35
30
55-64
65-74
75-84
> 85
25
20
15
10
5
0
STEMI
NSTEMI
UA
Hospital outcome among
different age groups: GRACE
30
25
20
55-64
65-74
75-84
> 85
15
10
5
0
HF
Shock
Major bleed
Hospital mortality associated with
increasing age: GRACE
16
Adjusted OR ( 95% CI )
14
12
10
55-64
65-74
75-84
> 85
8
6
4
2
0
Adjusted OR
55-64
65-74
75-84
> 85
2.77
4.95
8.04
15.7
(1.53 - 4.99)
(2.78 - 8.79)
(4.53 - 14.3)
(8.77 - 28.3)
Using GRACE risk model: SBP,
initial serum creatinine, HR,
cardiac enzyme, Kilip class STsegment deviation, cardiac
arrest at arrival
Hospital procedures: GRACE
60
50
40
55-64
65-74
75-84
> 85
30
20
10
0
Angio
PCI
CABG
Medications prescribed during
hospitalization: GRACE
100
90
80
70
60
50
40
30
20
10
0
55-64
65-74
75-84
> 85
ASA
Beta blockers
IIb/IIIa
Acute Coronary Syndrome:
Summary of Differences by Age
• Frequency of no anginal pain/atypical pain
as presenting symptom increased with age
• Frequency of ST-segment elevation on
admitting ECG decreased with age
• Use of acute reperfusion strategies
significantly declined with advancing age
• Seven-day, 30-day and 1-year mortality
increased with advancing age
Some factors contributing to worse
outcomes in elderly ACS patients
• More extensive CAD and higher risk of
previous MI
• Increased risk of complications including
heart failure, atrial fibrillation, ventricular
rupture, bleeding or stroke
Some factors contributing to worse
outcomes in elderly ACS patients
• Late presentation and/ or delayed
recognition due to atypical symptoms and
/or less classical ECG changes
• Reduced utilization of EBM strategies
• Increased co-morbidities, especially renal
insufficiency and pulmonary diseases
Results of Percutaneous Coronary
Interventions (PCI) in the Elderly
• Data from ACC national registry
• 8828 PCI procedures performed on
octogenarians (mean age 83.7 yrs)
J Am Coll Cardiol 2002; 40: 394-402
Results of Percutaneous Coronary
Interventions (PCI) in the Elderly
• 93% angiographic success rate
• 3.77% in-hospital mortality rate (1.35% inhospital mortality rate if no MI in the week
preceding PCI
• Most important predictor of in-hospital
mortality was presence of an acute MI and
time after MI
CABG surgery in the elderly
Elderly patients have a higher incidence of:
• Left main disease
• Multi-vessel disease
• LV dysfunction
• Re-operation as an indication for surgery
• Concomitant valvular heart disease
• Additional co-morbidities
Post-op course in the elderly
Combination of more advanced CAD and
worse co-morbidities leads to increased
mortality and higher rates of:
•
•
•
•
•
Intra-operative and post-operative MI
Low output state and use of IABP
Stroke, GI complications
Wound infections
Renal failure
Heart failure
HF in women: 10 year incidence
rates/1000 person-years (CHS)
40
35
30
25
65-69
70-74
75-79
80-84
20
15
10
5
0
Caucasian
African American
HF in men: 10 year incidence
rates/1000 person-years (CHS)
60
50
40
65-69
70-74
75-79
80-84
30
20
10
0
Caucasian
African American
Increasing prevalence of heart failure
over past 20 years
6
5
4
3
# of HF pts in millions
2
1
0
1983
1988
1993
1998
2003
Major Public Health Problem
• 5 million US patients have heart failure with
550,000 newly diagnosed cases/year
• HF accounts for 12-15 million office visits
and 6.5 million hospital days each year
• 53,000 deaths/year from HF as primary
cause and number steadily rising
www.acc.org/clinical/guidelines/failure//index.pdf.
Heart failure is predominately
a disease of the elderly
• 6-10% of patients over age 65 have HF.
• Approximately 80% of patients hospitalized
with HF are over age 65.
• HF is the most common Medicare DRG.
• More $$ spent for diagnosis and treatment
of HF than for any other diagnosis
Some potential reasons for the high
prevalence of HF in the elderly
• Age-related changes in ventricular function
(particularly diastolic function)
• Cumulative effects of hypertension and
other cardiovascular disease risk factors.
www.acc.org/clinical/guidelines/failure//index.pdf.
Some potential reasons for the high
prevalence of HF in the elderly
• Less aggressive treatment of some
cardiovascular risk factors in the elderly.
• Elderly patients may often take medications
that exacerbate HF symptoms.
www.acc.org/clinical/guidelines/failure//index.pdf.
Heart failure in the elderly
• Like ACS, heart failure is often under
recognized and inadequately treated in
elderly patients.
• Elderly HF patients may present with
atypical symptoms & physical exam
findings.
www.acc.org/clinical/guidelines/failure//index.pdf.
Heart failure symptoms in the elderly
Less common
• Dyspnea and orthopnea
More common
• Daytime oliguria & nocturia
• Confusion, insomnia, irritability
• Anorexia and GI disturbances
• Non-specific complaints (often misdiagnosed as
concomitant disease or age-related changes)
Tresch
Systolic function by gender among
CHS participants with HF
(Am J Cardiol 2001; 87: 413-419)
HF in older vs. younger patients
Characteristic
Middle-aged
Elderly
Prevalence
Gender
Etiology
LVEF
Co-morbidities
< 1%
M>W
CHD
Impaired
Fewer
6-10%
W>M
Hypertension
Preserved
Multiple
Am J Geriatric Cardiol 2001; 9 (suppl) 97-111
Differential diagnosis of HF in
patients with preserved LV function
• Incorrect diagnosis
• Inaccurate measurement of LV ejection fx
• Primary valvular disease
• Restrictive cardiomyopathy
• Pericardial constriction
www.acc.org/clinical/guidelines/failure//index.pdf
Differential diagnosis of HF in
patients with preserved LV function
• Episodic/reversible LV systolic dysfunction
• Severe hypertension
• HF associated with high metabolic demand
• COPD with right heart failure
• Pulmonary hypertension with pulmonary
vascular disorders
Impact of age and gender on
normal reference BNP levels
70
60
50
40
Men
Women
30
20
10
0
45-54
55-64
65-74
> 74
Pharmacologic therapy for
chronic systolic heart failure
Diuretics
Digoxin
ACE-I
Beta-blockers
ARB
Anti-aldosterone
Isordil/hydralazine
Improved symptoms
Improved morbidity
Improved morbidity & mortality
Improved morbidity & mortality
Improved morbidity & mortality
Improved morbidity & mortality
Improved morbidity & mortality
Principles of treating patients
with diastolic dysfunction
• Control hypertension
• Control tachycardia
• Reduce central blood volume
• Alleviate myocardial ischemia
CHARM-Preserved Trial
• 3023 patients (mean age 67 yrs) with Class
II-IV heart failure and LVEF > 40%
• Randomly assigned to placebo versus
candesartan (target daily dose = 32 mg)
• at 6 months, 2/3 of study patients achieved
target treatment dose
CHARM-Preserved Trial
• Primary outcome = cardiovascular death or
admission to hospital for HF.
• Median follow-up = 36 months
Number of HF admissions
during CHARM-Preserved Trial
20
18
16
14
12
10
8
6
4
2
0
Placebo
Candesartan
1
2
3 or more
total
Angiotensin receptor blockers in HF
• Use of an ARB could be considered in
patients with an ejection fraction > 40% to
reduce the risk of hospitalization due to
heart failure.
Lancet 2003; 362: 754-755
Valvular heart disease
2006 Updated Guidelines for Management
of Patients with Valvular Heart Disease
• Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr.,
Faxon DP, et al. ACC/AHA 2006 guidelines for the
management of patients with valvular heart disease:
executive summary: a report of the American College of
Cardiology/American Heart Association Task Force on
Practice Guidelines (Writing Committee to Revise the
1998 Guidelines for the Management of Patients with
Valvular Heart Disease). Circulation 2006; 114: 450-527.
also available online at http:// www.circulationaha.org
Morphologic changes of elderly hearts
Necropsy findings in 93 patients > 90 yrs.
Finding
Calcified aortic valve cusps
Calcified mitral annulus
Calcified papillary muscle
% of patients
63
45
45
Roberts WC. Morphological features of the elderly heart in
Cardiovascular Disease in the Elderly 3rd edition,
Aronow WS, Fleg JL (eds) Marcel Dekker 2004
Cardiovascular Health Study:
Prevalence of aortic sclerosis
60
50
40
Women
Men
30
20
10
0
65-74
75-84
85+
Cardiovascular Health Study:
Prevalence of aortic stenosis
7
6
5
4
Women
Men
3
2
1
0
65-74
75-84
85+
Differences between young and
old patients with valvular AS
Characteristic
Sex
Etiology
Valve
Commissural fusion
Systemic BP
Pulse pressure
Carotid upstroke
Palpable LVH
Young patientsOlder patients
males > females
males = females
congenital or RHD calcific degen
bicuspid
tricuspid
yes
no
usually low
normal/ increase
narrow
frequently wide
diminished, slow
normal
common
uncommon
Differences between young and
old patients with valvular AS
Characteristic
Young patientsOlder patients
Thrill
Ejection click
S4
Systolic murmur
Location
Atrial fibrillation
AV calcium
common
common
common
harsh, rough
upper sternum
rare
variable
uncommon
uncommon
common
musical
apical
25 %
common
Tresch
Clinical features of AS and
their positive predictive value
Features
Likelihood ratios
Slow rate of rise of carotid pulse
2.8 – 130
Mid to late peaking murmur
8.0 – 101
Decreased intensity of S2
3.1 – 50
JAMA 1997; 277: 564-571
Correlation of physical exam with
severity of AS in elderly patients
Exam finding
ASEM
Prolonged SM
Late-peak SM
Prolonged carotid
A2 decreased/absent
Mild
95
3
3
3
5
Moderate
100
63
63
33
49
Severe
100
84
84
53
74
Am J Cardiol 1991; 67: 776-777
Event rates per 1000 person-years for
patients with sclerotic aortic valves
Otto CM, et al. N Engl J Med 1999; 341: 142-147
40
35
30
25
normal
sclerosis
20
15
10
5
0
stroke
HF
MI
CV death All death
Treatment of aortic stenosis
• Therapeutic decisions in patients with AS
are based primarily on presence or absence
of symptoms.
• After onset of symptoms (angina, heart
failure or syncope) average survival is
typically less than 2-3 years
• AVR is the only effective Rx for severe AS
Special considerations in elderly
patients undergoing valve surgery
Aortic stenosis
• AVR should be considered in all elderly patients
with symptoms caused by aortic stenosis.
• Balloon valvotomy is not an acceptable alternative
to aortic valve replacement.
• Concomitant CAD and/or LV dysfunction are
predictive of worse outcomes.
Special considerations in elderly
patients undergoing valve surgery
Aortic stenosis
• Some elderly females have a narrow LV outflow
tract & small annulus that may need enlargement.
• Heavy calcification of aortic valve, annulus or
aortic root may require surgical debridement.
• Excessive or inappropriate LVH may increase risk
of peri-operative morbidity and mortality.
Circulation 2006; 114: 450-527.
Special considerations in elderly
patients undergoing valve surgery
Aortic regurgitation
• Pure AR is uncommon in elderly patients.
• Patients > 75 are more likely to develop symptoms
or LV dysfunction at earlier stages of LV dilatation
and may display more persistent LV dysfunction
and HF symptoms after surgery.
• Elderly patients with AR have worse postoperative survival rates than younger patients.
Mitral regurgitation (MR)
• Myxomatous degeneration and mitral
annular calcification (MAC) are common
etiologies for MR in the elderly.
• Patients with MR may remain symptom free
for many years (average interval from
diagnosis to onset of symptoms = 16 years).
• Most patients with chronic MR have mild mod symptoms and unlikely to need MVR.
Marked increased prevalence of
MAC in elderly patients
70
60
50
40
Men
Women
30
20
10
0
62-70
71-80
81-90
Clinical characteristics of subjects
with MAC: Framingham Heart Study
• Older females with higher BMI
• Higher SBP and more LVH on ECG
• Increased % with diabetes, hyperlipidemia
• More likely to have prevalent atrial
fibrillation, heart failure and CVD
Circulation 2003; 107: 1492-1496
Potential complications of
mitral annular calcification
•
Conduction system disease
•
Arrhythmia, especially atrial fibrillation
•
Systemic emboli
•
Mitral regurgitation
•
Acquired mitral stenosis
•
Infective endocarditis
Association of MAC with
incidence of CV disease
Incidence rates per 10,000 person-years
16 yrs of follow-up (adjusted for age and sex)
Condition
No MAC
MAC
Myocardial infarction
Heart failure
Incident CVD
CV death
All-cause death
113
153
268
162
443
225
383
554
428
847
(Circulation 2003: 107: 1492-1496)
Mitral annular calcification predicts
CV morbidity and mortality
900
800
700
600
500
No MAC
MAC
400
300
200
100
0
MI
HF
CV death
all death
Are MAC and aortic valve sclerosis
(ASc) markers of subclinical CVD ?
• Vascular calcification is associated with CV
risk factors & incident CV events
• Burden of shared risk factors including age,
HTN, DM, hyperlipidemia and obesity
• MAC and ASc may function as bioassay for
longitudinal exposure to CV risk factors.
Features of MVP in the elderly
• Isolated systolic clicks are rare
• Holosystolic murmurs are common
• Degree of regurgitation more severe c/w
younger patients
• Echo findings of pansystolic prolapse and
flail valve leaflets are common
Features of MVP in the elderly
• Heart failure is a a problem, especially in
elderly men with MVP
• Onset of heart failure may be abrupt
• At time of surgery, many patients have
ruptured chordae
Special considerations in elderly
patients undergoing valve surgery
• Elderly patients with MR fare less well with
valve surgery than do patients with AS.
• Operative mortality increases and survival
is reduced in patients > 75 years, especially
if valve replacement (versus repair) is
performed or CAD is also present.
Atrial fibrillation
2006 Updated Guidelines for
Management of Patients with
Atrial Fibrillation
• Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, et
al. ACC/AHA/ESC 2006 guidelines for the management of
patients with atrial fibrillation-executive summary: a
report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines and
the European Society of Cardiology Committee for
Practice Guidelines ( Writing Committee to Revise the
2001 Guidelines for the Management of Patients with
Atrial Fibrillation). Circulation 2006; 114: 700-752. also
available online at http:// www.circulationaha.org
Atrial fibrillation
• Prevalence increases with advancing age
(6-8% of those over age 80 have AF)
• Age-adjusted incidence is higher in men
• Blacks have less than ½ the age-adjusted
risk of developing AF c/w whites
• Prevalence of AF increases with severity of
HF or valve disease
Prevalence of atrial fibrillation
in US adults (ATRIA Study)
• Approximately 2.3 x 106 US adults have AF
• By 2050, the number of US adults with AF
is projected to increase to 5.6 million
– More than 50% of affected individuals
will be 80 years of age or older
JAMA 2001; 285: 2370-2375
Atrial Fibrillation Follow-Up
Investigation of Rhythm Management
(AFFIRM) Trial
Randomized multi-center trial of two
approaches to the Rx of atrial fibrillation:
• Cardioversion and treatment with antiarrhythmic drugs to maintain NSR; or
• Allow atrial fibrillation to persist but control
heart rate
• Use of anticoagulant drugs was
recommended in both approaches
AFFIRM Trial
• 4060 patients (mean age 69.7 yrs)
• Male/Female ratio of 60/40
• Underlying cardiac diagnoses
– Hypertension
– Heart failure
– % with normal LVEF
51%
23%
74%
AFFIRM Trial: Summary of Results
• Rhythm control strategy offered no survival
advantage c/w rate control strategy (5-year
mortality 23.8% vs. 21.3%)
• Fewer hospitalizations in rate control group
(73% vs. 80%, P <.001) and fewer adverse
drug effects than rhythm control group
N Engl J Med 2003: 347: 1825-1833
Risk stratification in AF patients
using the CHADS 2 risk score
Risk factors
C Recent congestive heart failure
H Hypertension
A Age > 75 years
D Diabetes mellitus
S2 History of stroke or TIA
Score
1
1
1
1
2
J Am Coll Cardiol 2004; 43: 929-935
CHADS2 risk score and
adjusted stroke rate in NRAF
20
18
16
14
12
10
8
6
4
2
0
CHADS 2 score
0
1
2
3
4
5
6
Potential reasons for increased
warfarin sensitivity in the elderly
•
•
•
•
•
•
Concurrent drug therapy
Heart failure
Advanced malignancy
Malnutrition
Diarrhea
Unsuspected vitamin K deficiency
Hepatic abnormalities may increase
warfarin sensitivity in the elderly
• Decreased synthesis of vitamin K dependent
clotting factors
• Diminished albumin concentration
(increases unbound fraction of warfarin)
• Reduced intrinsic clearance of drug and/or
decline in racemic warfarin clearance
• Decreased liver size
Additional background slides
Effects of aging on the CV system
Summary of principal effects
of aging on cardiovascular system
• Increased arterial and myocardial stiffness
• Impaired beta adrenergic responsiveness
• Impaired endothelial function
• Reduced sinus node function
• Decreased baroreceptor responsiveness
• Net effect is marked reduction in CV reserve
www.sgcard.org
Clinical implications
• Increased SBP and pulse pressure
• Increased prevalence of atrial fibrillation
• Increased prevalence of heart failure,
especially HF with preserved LV function
www.sgcard.org
Clinical implications
• Increased prevalence of bradyarrhythmias
and “sick sinus syndrome”
• Increased risk for syncope and falls
• Impaired response to stress/illness
www.sgcard.org
Arterial changes with aging
• Increased calcium, collagen & collagen cross-links
• Increased intima-medial thickness
• Increased vessel diameter
• Decreased elastin
• Increased systolic BP and pulse pressure
• Increased vascular stiffness indices and pulse
wave velocity
• Net effect is increase in afterload
Endothelial function and aging
• Marked decline in endothelium-mediated
vasodilation from age 40-70
• No change in vasodilator response to
nitroglycerine
• Age-related effects on endothelial function
are exacerbated by HTN, dyslipidemia,
CAD and HF. These effects are attenuated
by regular aerobic exercise.
Effect of age on stroke volume
and LVEF with exercise
• Impaired LV emptying with increased ESV index
• Impaired LV filling with minimal change in EDV
• Net effect: decrease in both stroke volume and LV
ejection fraction
• LVEF at peak exercise declines from 85% in 20’s
to 70% in 80’s
• Augmentation in EF from rest to peak exercise
declines with age
CV changes during maximum upright
exercise between ages 20 and 80
Oxygen consumption
AVO2 difference
Cardiac output
Heart rate
LV stroke volume
LVEDV
LVESV
LV ejection fraction
reduced ~ 50 %
reduced ~ 25 %
reduced ~ 25 %
reduced ~ 25 %
reduced ~ 15 - 25 %
NC/slight decrease
increased ~ 150%
reduced ~ 15%
Changes on resting echo comparing
normal subjects ages 20 and 80
LV wall thickness
LV end diastolic diameter
LV end systolic diameter
Fractional shortening
Peak E-wave velocity
Peak A-wave velocity
LA dimension
Increased by ~ 30%
No change
No change
No change
Reduced ~ 50 %
Increased ~ 50 %
Increased ~ 10 %
Circulation 1977; 56: 273-278
Effect of aging on diastolic function
• Decrease in elastic properties of heart and
great vessels (SBP, myocardial stiffness)
• Decrease in rate of ventricular filling
• Increase in cardiac fibrosis
• Decline in active relaxation
• Decrease in beta receptor density
• Decline in peripheral vasodilatory capacity
Effect of aging on conduction system
• Increased elastic tissue and collagen
• Marked decrease SA node pacemaker cells
• Calcification of cardiac skeleton
• Slowed conduction in AV node and proximal HisPurkinje system
• Conduction abnormalities amplified by
hypertension, CAD and amyloid infiltration
ECG changes associated with aging
• Modest increase in PR and QT intervals
• Left shift in QRS axis
• Increased prevalence of RBBB
• Flattening of the ST segment
• Decreased T-wave amplitude
• No significant change in resting heart rate but
marked reduction in HR variability
www.sgcard.org
Arrhythmias in the Elderly
• Marked increase in frequency of SVT and PVCs
• Short runs of SVT occur in 1/3 of healthy older
subjects on 24 hour ambulatory monitoring
• Ventricular couplets occur in ~ 11% and short runs
of NSVT occur in about ~ 4% of healthy persons
> 60 years of age
• In the absence of heart disease, none of these
arrhythmias are associated with adverse prognosis
Am J Cardiol 1992; 70: 748-751