Download Current Thinking in Acute Congestive Heart Failure and Pulmonary

Reference Section
Current Thinking in Acute Congestive Hear t Failure and Pulmonar y Edema
a report by
Shamai A Grossman
Director, The Cardiac Emergency Center and Clinical Decision Unit, Department of Emergency Medicine,
Beth Israel Deaconess Center Instructor of Medicine, Harvard Medical School
Dr Shamai A Grossman serves on
the faculty of Harvard Medical
School and is actively involved in
both medical and postgraduate
training, lecturing and teaching in
various capacities on a daily basis.
In addition, he is heavily sought
after through invited lectureships.
Dr Grossman spearheaded the
development of the Clinical Decision
Unit and Cardiac Emergency Center
at Beth Israel Deaconess Medical
Center, and has served as medical
director of this observation and
management unit since its inception.
Dr Grossman’s research has focused
on developing evidence-based
guidelines for the management of
cardiac emergencies and consistently
presents his work at national
meetings. Dr Grossman trained as
both a cardiologist and emergency
physician and has published
extensively on cardiac issues in
emergency medicine.
Introduction
Congestive heart failure (CHF) is an imbalance in pump
function in which the heart fails to maintain the
circulation of blood adequately. The most severe
manifestation of CHF, pulmonary edema, develops when
this imbalance causes an increase in lung fluid secondary
to leakage from pulmonary capillaries into the
interstitium and alveoli of the lung.
CHF can be categorized as forward or backward
ventricular failure. Backward failure is secondary to
elevated systemic venous pressure, while left ventricular
failure is secondary to reduced forward flow into the aorta
and systemic circulation. Furthermore, heart failure can
be subdivided into systolic and diastolic dysfunction.
Systolic dysfunction is characterized by a dilated left
ventricle with impaired contractility, while diastolic
dysfunction occurs in a normal or intact left ventricle with
impaired ability to relax and receive as well as eject blood.
The New York Heart Association’s (NYHA’s) functional
classification of CHF is one of the most useful. Class I
describes a patient who is not limited with normal
physical activity by symptoms. Class II occurs when
ordinary physical activity results in fatigue, dyspnea, or
other symptoms. Class III is characterized by a marked
limitation in normal physical activity. Class IV is defined
by symptoms at rest or with any physical activity.
CHF is best summarized as an imbalance in starling forces
or an imbalance in the degree of end-diastolic fiber
stretch proportional to the systolic mechanical work
expended in an ensuing contraction.This imbalance may
be characterized as a malfunction between the
mechanisms that keep the interstitium and alveoli dry and
the opposing forces that are responsible for fluid transfer
to the interstitium.
1
Maintenance of plasma oncotic pressure (generally
about 25mmHg) higher than pulmonary capillary
pressure (about 7–12mmHg), maintenance of
connective tissue and cellular barriers relatively
impermeable to plasma proteins, and maintenance of an
extensive lymphatic system are the mechanisms that
keep the interstitium and alveoli dry.
Opposing forces responsible for fluid transfer to the
interstitium include pulmonary capillary pressure and
plasma oncotic pressure. Under normal circumstances,
when fluid is transferred into the lung interstitium with
increased lymphatic flow, no increase in interstitial
volume occurs. When the capacity of lymphatic
drainage is exceeded, however, liquid accumulates in the
interstitial spaces surrounding the bronchioles and lung
vasculature, thus creating CHF.When increased fluid and
pressure cause tracking into the interstitial space around
the alveoli and disruption of alveolar membrane
junctions, fluid floods the alveoli and leads to pulmonary
edema. The etiologies of pulmonary edema can be
placed in the following categories.
• Pulmonary edema secondary to altered capillary
permeability – this category includes acute respiratory
deficiency syndrome (ARDS), infectious causes,
inhaled toxins, circulating exogenous toxins, vasoactive
substances, disseminated intravascular coagulopathy
(DIC), immunologic processes reactions, uremia, near
drowning, and other aspirations.
• Pulmonary edema secondary to increased
pulmonary capillary pressure – this comprises
cardiac causes and noncardiac causes, including
pulmonary venous thrombosis, stenosis or venoocclusive disease, and volume overload. Pulmonary
edema may be secondary to decreased oncotic
pressure found with hypoalbuminemia, and can be
secondary to lymphatic insufficiency. It can also
occur secondary to large negative pleural pressure
with increased end expiratory volume.
• Pulmonary edema secondary to mixed or unknown
mechanisms including high altitude pulmonary edema
(HAPE), neurogenic pulmonary edema, heroin or
other overdoses, pulmonary embolism, eclampsia,
postcardioversion, postanesthetic, postextubation, and
post-cardiopulmonary bypass.
Epidemiology
In the US, more than three million people have CHF, and
more than 400,000 new cases present yearly. The
prevalence of CHF is 1% to 2% of the general population.
BUSINESS BRIEFING: US CARDIOLOGY 2004
Current Thinking in Acute Congestive Hear t Failure and Pulmonar y Edema
Approximately 30% to 40% of patients with CHF are
hospitalized every year. CHF is the leading diagnosisrelated group (DRG) among hospitalized patients older
than 65 years. The five-year mortality after diagnosis
was reported as 60% in men and 45% in women in
1971. In 1991, data from the Framingham Heart Study
showed the five-year mortality rate for CHF essentially
remaining unchanged, with a median survival of 3.2
years for males and 5.4 years for females. This may be
secondary to an aging US population with declining
mortality due to other diseases.
The most common cause of death is progressive heart
failure, but sudden death may account for up to 45% of
all deaths. After auditing data on 4,606 patients
hospitalized with CHF between 1992 and 1993, the
total in-hospital mortality rate was 19%, with 30% of
deaths occurring from noncardiac causes. Patients with
coexisting insulin-dependent diabetes mellitus have a
significantly increased mortality rate.
African-American patients are 1.5 times more likely to
die of CHF than white patients. Nevertheless, AfricanAmerican patients appear to have similar or lower inhospital mortality rates than white patients. The
incidence is greater in males than in females for patients
aged 40–75 years. No sex predilection exists for patients
older than 75 years. The overall incidence of CHF
increases with increasing age and effects about 10% of
the population older than 75 years.
Diagnostic Modalities
History
History of presenting illness is crucial in the evaluation
of patients with acute CHF exacerbations and
pulmonary edema.
A variety of cardiac diseases cause CHF and pulmonary
edema and initial evaluation questions should reflect
these processes.The most common cause of heart failure
is coronary artery disease, which is secondary to loss of
left ventricular muscle, on-going ischemia, or decreased
diastolic ventricular compliance. Other disease processes
include hypertension, valvular heart disease, congenital
heart disease, other cardiomyopathies, myocarditis, and
infectious endocarditis.
CHF is often precipitated by cardiac ischemia or
dysrhythmias, cardiac or extracardiac infection,
pulmonary embolus, physical or environmental
stresses, changes or noncompliance with medical
therapy, dietary indiscretion, or iatrogenic volume
overload. Systemic processes such as pregnancy and
hyperthyroidism as precipitants of CHF should also
be considered.
BUSINESS BRIEFING: US CARDIOLOGY 2004
The differential diagnosis for acute CHF exacerbation
and pulmonary edema is broad and should include
acute respiratory distress syndrome (ARDS), altitude
illness, anaphalaxsis, anemia, bronchitis, chronic
obstructive pulmonary disease and non cardiac
asthma, dysbarism, hyperventilation syndrome,
pericarditis and cardiac tamponade, pneumonia,
pneumthorax and pneumomediastinum, septic shock,
and venous air embolism.
Dyspnea on exertion has been found to be the most
sensitive complaint, yet the specificity for dyspnea is less
than 60%. Orthopnea and paroxysmal nocturnal
dyspnea (PND) are relativly common symptoms;
however, the sensitivity for orthopnea and PND is only
20% to 30%. A cough producing pink, frothy sputum is
highly suggestive of CHF. Other common presenting
complaints include dyspnea at rest, edema, often
localized to the lower extremities, and anxiety. Less
specific complaints may include weakness,
lightheadedness, abdominal pain, malaise, wheezing, and
nausea. Past medical history will often include
cardiomyopathy, valvular heart disease, alcohol use,
hypertension, angina, prior myocardial infarction, and
familial heart disease.
Physical Examination
Findings such as peripheral edema, jugular venous
distention, and tachycardia are highly predictive of
CHF. Overall, specificity of physical examination has
been reported at 90%; however, this same study
reported a sensitivity of only 10% to 30%. Initial
physical findings may include:
•
•
•
•
tachypnea;
utlization of accessory muscles of respiration;
hypertension; and
pulsus alternans (alternating weak and strong pulse
indicative of depressed left ventricle function).
Skin may be diaphoretic or cold, gray, and cyanotic.
Jugular venous distention (JVD) is frequently present.
Wheezing or rales may be heard on lung auscultation.
The apical impulse is often displaced laterally. Cardiac
auscultation may reveal aortic or mitral valvular
abnormalities, S3 or S4. Lower extremity edema may
also be noted, especially in the subacute process.
Laboratory Studies
Until recently, differentiating asthma and other
pulmonary disease has been difficult in the acute
setting, particularly due to the poor sensitivities and
specificities of most elements of history and physical
examination. The standard of care has been shotgun
therapy, namely treating patients for both CHF and an
2
Reference Section
acute pulmonary process such as asthma, with both
diuretics and beta agonists.The Breathing Not Properly
Study has suggested that serum levels of beta naturietic
peptide (BNP) and the BNP precursor, Pro-BNP can
help identify CHF as the origin of acute dyspnea.This
study found sensitivities of 90% with specificities of
76%. Positive predictive value was 79% with a negative
predictive value of 89%.
Mueller found a reduction in hospital length of stay of
three days when BNP levels were utilized. However,
this study assumed an average length of stay of 11 days.18
The average length of stay in the US for CHF
exacerbations is approximately four days. In addition,
although the time to initiation of therapy was reduced
in this study from 90 to 60 minutes, the general practice
in the US is immediate initiation of shotgun therapy.
In the primary care setting, Wright identified 305
patients with heart failure and revaluated them with or
without the Pro-BNP result.20 Diagnostic accuracy
improved from 52% to 60% without Pro-BNP, and from
49% to 70% with Pro-BNP. Maisel identified in the
Breathing Not Properly Study a 20% increase in patients
with CHF, who presented with dyspnea and a history of
asthma or COPD, but no prior history of CHF.17
BNP is available as a point-of-care test, with results
available within 15 minutes. However, only Pro-BNP
can be utilized concomitantly with Nesiritide.
Serum levels of BNP of <100pg/ml are unlikely to be
from CHF. In the Breathing Not Properly Study, BNP
of 50pg/ml increased sensitivity from 90% to 97% at a
cost of reducing specificity. Levels of 100–500pg/ml
may be CHF. However, other conditions that also
elevate right filling pressures such as pulmonary
embolus, primary pulmonary hypertension, end stage
renal failure, cirrhosis and hormone replacement
therapy may also cause elevated BNP levels in this
range. BNP levels of >500pg/ml are most consistent
with CHF.
Other serum laboratory values may identify prerenal
azotemia or elevated alanine aminotransferase (ALT),
aspartate aminotransferase (AST), or bilirubin,
suggestive of a congestive hepatopathy. Mild azotemia,
decreased erythrocyte sedimentation rate (ESR), and
proteinuria are observed in early and mild-to-moderate
disease. Increased creatinine, hyperbilirubinemia, and
dilutional hyponatremia are observed in severe cases.
3
Cardiac enzymes and other serum markers for ischemia
or infarction may be useful as well. Arterial blood gas
(ABG) may be of benefit in evaluation of hypoxemia,
ventilation/perfusion (V/Q) mismatch, hypercapnia,
and acidosis.
Imaging Studies
Although imaging tests are of limited benefit in acute
CHF, chest X-ray (CXR) is the most useful tool.
Cardiomegaly may be observed with a cardiothoracic
ratio greater than 50%. Pleural effusions may be present
bilaterally or, if they are unilateral, are more commonly
observed on the right. Early CHF may manifest as
cephalization of pulmonary vessels, generally reflecting a
pulmonary capillary wedge pressure (PCWP) of
12–18mmHg. As the interstitial fluid accumulates, more
advanced CHF may be demonstrated by Kerley B lines
(PCWP: 18–25mmHg). Pulmonary edema is observed
as perihilar infiltrates often in the classic butterfly pattern
reflecting a PCWP greater than 25mmHg.
Several limitations exist in the use of chest X-rays when
attempting to diagnose CHF. Classic radiographic
progression often is not found, and as much as a 12hour radiographic lag from onset of symptoms may
occur. In addition, radiographic findings frequently
persist for several days despite clinical recovery.
Emergency transthoracic echocardiography (ECHO)
may help identify regional wall motion abnormalities as
well as globally depressed or myopathic left ventricular
function. ECHO may help identify cardiac tamponade,
pericardial constriction, and pulmonary embolus.
ECHO also is useful in identifying valvular heart
disease, such as mitral or aortic stenosis or regurgitation.
Electrocardiogram (ECG) is a non-specific tool but
may be useful in diagnosing concomitant cardiac
ischemia, prior myocardial infarction (MI), cardiac
dysrhythmias, chronic hypertension, and other causes of
left ventricular hypertrophy.
Procedures
No defined role exists for invasive monitoring devices
such as central venous placement (CVP) lines. Timeconsuming placement of pulmonary artery catheters
has not been shown to prolong survival, even in the
coronary care unit and, thus far, has not been well
studied in the ED setting. Cardiac catheterization may
be necessary for a complete evaluation, treatment and
assessment of prognosis.
In patients refractory to medical therapy or with
evidence of cardiogenic shock, cardiac catheterization,
angioplasty, coronary bypass, or intra-aortic balloon
pump (IABP) may be helpful.
Emergency Care
Management of a patient presenting with signs and
symptoms of CHF and pulmonary edema with the
ABCs should begin with administration of
BUSINESS BRIEFING: US CARDIOLOGY 2004
Current Thinking in Acute Congestive Hear t Failure and Pulmonar y Edema
supplemental oxygen, initially 100% non-rebreather
facemask. Cardiac monitoring and continuous pulse
oximetry must also be utilized, and intravenous (IV)
access obtained. To reduce venous return, the head of
the bed should be elevated. Patients may be most
comfortable in a sitting position with their legs
dangling over the side of the bed, which allows for
reduced venous return and decreased preload.
Therapy generally starts with nitrates and diuretics if
patients are hemodynamically stable. Many other
treatment modalities may play some role in acute
management. If possible, the underlying cause should
be treated as well.This is particularly true for patients
with known diastolic dysfunction who respond best
to reductions in blood pressure rather than to
diuretics, nitrates, and inotropic agents. Contributing
factors must be eliminated where possible, and fluid
and sodium restricted.
Recent data comparing nasal CPAP therapy with
facemask ventilation therapy has demonstrated a
decreased need for intubation rates when these
modalities are used. In patients with severe CHF treated
with CPAP, however, no significant difference was found
in short-term mortality and hospital stay. Although
BiPAP therapy may improve ventilation and vital signs
more rapidly then CPAP, a higher incidence of MI
associated with BiPAP has been reported. BiPAP and
CPAP are contraindicated in the presence of acute facial
trauma, the absence of an intact airway, and in patients
with an altered mental status or who are uncooperative.
Medication
The goal of pharmacotherapy is to achieve a PCWP of
15–18mmHg and a cardiac index >2.2L/min/m2,
while maintaining adequate blood pressure and
perfusion to essential organs. These goals may need to
be modified for some patients.
Use of diuretics, nitrates, analgesics, and inotropic
agents are indicated for the treatment of CHF and
pulmonary edema. Calcium channel blockers, such as
nifedipine and nondihydropyridines, increase mortality
and increase incidence of recurrent CHF with chronic
use. Conflicting evidence currently exists in favor as
well as against the use of calcium channel blockers in
the acute setting – at this time is limited to acute use
in patients with diastolic dysfunction and heart failure,
a condition not easily determined in the emergency
department (ED).
First-line therapy generally includes a loop diuretic such
as furosemide, which will inhibit sodium chloride
reabsorption in the ascending loop of Henle. Loop
diuretics should be administere IV, since this allows for
BUSINESS BRIEFING: US CARDIOLOGY 2004
both superior potency and higher peak concentration
despite increased incidence of side-effects, particularly
ototoxicity. Higher doses and more rapid redosing may be
appropriate for the patient in severe distress. Metolazone
and chlorothiazide have been used as adjunctive therapy
in patients initially refractory to furosemide.
Nitrates reduce myocardial oxygen demand by lowering
preload and afterload. Nitoglycerin is particularly useful in
the patient who presents with acute pulmonary edema
with a systolic blood pressure of at least 100mmHg.
However, oral nitrates, due to delayed absorption, have
little role in the acute presentations of CHF.
Morphine IV is an excellent adjunct in acute therapy.
In addition to being both an anxiolytic and an
analgesic, its most important effect is venodilation,
which reduces preload. Morphine also causes arterial
dilatation, which reduces systemic vascular resistance
(SVR) and increases cardiac output. Narcan can also
reverse the effects of morphine. However, some
evidence indicates that morphine use in acute
pulmonary edema may increase the intubation rate.
Angiotensin converting enzyme (ACE) inhibitors, such
as SL captopril or IV enalapril, may rapidly reverse
hemodynamic instability and symptoms, possibly
avoiding an otherwise imminent intubation. Haude
compared 25mg of SL captopril with 0.8mg of
sublingual nitroglycerin in 24 patients with class III and
class IV CHF and found that captopril induces a more
sustained and more pronounced improvement in
hemodynamics. Annane gave 1mg of IV enalapril to 20
patients presenting with acute class III and class IV CHF
over two hours and demonstrated rapid hemodynamic
improvement with no significant adverse effects on
cardiac output or hepatosplanchnic measurements.
Captopril may play a unique role in sustaining patients
with renal failure and concomitant acute CHF while
awaiting definitive therapy with dialysis. Since the
information on this subject is still controversial and
limited to small studies, their routine use cannot be
recommended at this time. ACE inhibitors remain a
promising area in need of further study.
Beta-blockers, possibly by restoring beta-1 receptor
activity or via prevention of catecholamine activity,
appear to be cardioprotective in patients with depressed
left ventricular function. The US Carvedilol Heart
Failure study group demonstrated a two-thirds decrease
in mortality in patients taking carvedilol with left
ventricular ejection fractions of 35% or less. Betablockers, particularly carvedilol, have been shown to
improve symptoms in patients with moderate-to-severe
heart failure. The role of beta-blockers in the acute
setting, however, is currently unclear – use should be
4
Reference Section
limited until hemodynamic studies indicate that further
deterioration will not occur.
for those patients with pulmonary edema refractory to
initial diuretics, CPAP or BiPaP.
Because differentiating CHF and asthma exacerbations
is often difficult, treating both with the shotgun
approach often is employed, particularly as both may
cause bronchospasm.Aerosolized beta-2 agonists, which
are the more selective of beta-agonists, decrease
tachycardia, dysrhythmias, and cardiac work while
transiently enhancing cardiac function. Terbutaline has
been shown to be successful in this setting, as well as
albuterol, isoetharine, and bitolterol.
Digoxin has no role in the emergency management of
CHF due to delayed absorption and diminished efficacy
at times of increased sympathetic tone.Thus, it has little,
if any, benefit in the patient presenting concomitantly
with atrial fibrillation and rapid ventricular response.
Digoxin should be limited to chronic CHF in which its
role has been well established.
Roles of theophyline and aminophylline in the acute
setting must be limited. They are positive inotropic
agents mediated by an increase in catecholamines, and
they dilate coronaries and exert mild diuretic effects.
Nevertheless, they can exacerbate dysrhythmias by
increasing cardiac work.
Steroids, IV or oral (PO), have been shown to worsen
pre-existing heart failure due to systemic sodium
retention and volume expansion, hypokalemia, and
occasional hypertension. Inhaled steroids, due to their lack
of systemic side-effects, may be a reasonable option in this
confusing patient presentation. However, given their
delayed onset of action, they remain an area in need of
further study.
Human B-type natriuretic peptides such as Nesiritide
may decrease hospital length of stay by up to four days.
BNP binds to particulate guanylate cyclase receptor of
vascular smooth muscle and endothelial cells. Binding to
the receptor causes increase in cyclic GMP, which serves
as second messenger to dilate veins and arteries. BNP
reduces pulmonary capillary wedge pressure and improves
dyspnea in patients with acutely decompensated CHF.
Contraindications include systolic blood pressure
<90mmHg – patients suspected of having, or known to
have, low cardiac filling pressures, significant valvular
stenosis, restrictive or obstructive cardiomyopathy,
constrictive pericarditis, pericardial tamponade, and
conditions in which cardiac output is dependent upon
venous return.
Nesirtitide may affect renal function in patients whose
renal function may depend on activity of reninangiotensin-aldosterone system; it may cause
hypotension, ventricular tachycardia, non-sustained VT,
headache, abdominal pain, back pain, insomnia, anxiety,
angina pectoris, nausea, and vomiting. BNP in the
emergency setting should likely be reserved at this time,
Dopamine stimulates both adrenergic and dopaminergic
receptors. Hemodynamic effects depend on the dose.
Lower doses stimulate mainly dopaminergic receptors
that produce renal and mesenteric vasodilation. Cardiac
stimulation and renal vasodilation is produced by higher
doses. Dobutamine produces vasodilation and increases
inotropic state. At higher dosages it may cause an
increased heart rate, exacerbating myocardial ischemia.
Disposition
With few exceptions, patients presenting with acute
symptoms of CHF or pulmonary edema require hospital
admission. Many patients who respond rapidly to early
therapy may require only an observation unit admission
with telemetry monitoring if ischemic etiologies are
being considered. Criteria for discharge from the ED
include gradual onset of shortness of breath, rapid
response to therapy, oxygen saturation greater than 90%,
and acute coronary syndromes and MI unlikely as the
precipitating event.Those patients who require intubation
or remain with significant respiratory, hemodynamic,
and/or cardiovascular compromise often require intensive
units (ICU) or cardiac care units (CCU) admission.
Prognosis
Based on data from 4,606 patients hospitalized with
CHF between 1992 and 1993, total in-hospital
mortality was 19%, with 30% of deaths occurring from
noncardiac causes. These patients, however, were noted
to have had suboptimal use of proven efficacious
therapy, compared with those who survived
hospitalizations, particularly among women and the
elderly. Thirty-year data from the Framingham heart
Study demonstrated a median survival of 3.2 years for
males and 5.4 years for females. Results of initial
treatment are usually good, regardless of cause. Longterm prognosis is variable. Mortality rates range from
10% in patients with mild symptoms to 50% with
advanced, progressive symptoms. ■
Bibliography
5
1. Edwards J D, Grant P T and Plunkett P, “The hemodynamic effects of sublingual nitroglycerin spray in severe left ventricular
failure”, Intensive Care Med. (1989), 15: pp. 247–249.
BUSINESS BRIEFING: US CARDIOLOGY 2004
Current Thinking in Acute Congestive Hear t Failure and Pulmonar y Edema
2. Gordon H S, Harper D L and Rosenthal G E “Racial variation in predicted and observed in-hospital death:A regional analysis”,
JAMA (1996), 276: pp. 1,639–1,644.
3. Hamilton R J, Carter W and Galahger E J, “Rapid improvement of acute pulmonary edema with sublingual captopril”,
Academic Emergency Medicine (1996), 3: pp. 205–212.
4. Harlan W, Oberman A and Grimm R,“Chronic congestive heart failure in coronary artery disease: Clinical criteria”, Ann. Intern.
Med. (1977), 86: pp. 133–138.
5. Lin M,“Reappraisal of continuous positive airway pressure therapy in acute cardiogenic pulmonary edema”, Chest (1995), 107:
pp. 1,379–1,386.
6. Melandri G, Semprini and Branzi A, “Comparative hemodynamic effects of transdermal vs intravenous nitroglycerin in acute
myocardial infarction with elevated pulmonary artery pressure”, Eur. Heart J. (1990), pp. 649–655.
7. Polese A, Fiorenti C and Olivari M T,“Clinical use of nifedipine in acute pulmonary edema”, Am. J. Med. (1979), 66: pp.825–830.
8. Andersson B and Waagstein F, “Spectrum and outcome of congestive heart failure in a hospitalized population”, Am. Heart J.
(1993), Sep; 126 (3 Pt 1): pp. 632–640.
9. Annane D, Bellissant E and Pussard E, “Placebo-controlled, randomized, double-blind study of intravenous enalaprilat efficacy
and safety in acute cardiogenic pulmonary edema”, Circulation (1996), Sep 15; 94 (6): pp. 1,316–1,324.
10. Chen J T, “Radiographic diagnosis of heart failure”, Heart Dis. Stroke (1992), Mar-Apr; 1 (2): pp. 58–63.
11. Clinical Quality Improvement Network Investigators, “Mortality risk and patterns of practice in 4606 acute care patients with
congestive heart failure,The relative importance of age, sex, and medical therapy”, Arch. Intern. Med. (1996) Aug 12–26; 156
(15): pp. 1,669–1,673.
12. Connors A F, Jr, Speroff T, Dawson N V,“The effectiveness of right heart catheterization in the initial care of critically ill patients”,
JAMA (1996), 276: pp. 889–897.
13. Goldstein R E, Boccuzzi S J and Cruess D, “Diltiazem increases late onset congestive heart failure in post myocardial infarction
patients with early reduction in ejection fraction”, Circulation (1991), 83: pp. 52–60.
14. Kannel W B and Pinsky J L, “Trends in cardiac failure incidence and causes of three decades in the Framingham study”, J. Am.
Coll. Cardiol. (1991), 17: p. 87A.
15. Kiyingi A, Field M J and Pawsey C C,“Metalozone in treatment of severe refractory congestive cardiac failure”, Lancet (1990),
335: pp. 29–31
16. Kostuk W, Barr J W and Simon A L, “Correlations between the chest film and hemodynamics in acute myocardial infarction”,
Circulation (1973), 48: pp. 624–632.
17. Massie B M, “Congestive heart failure: Current controversies and future prospects”, Am. J. Cardiol. (1990).
18. Mehta S, Jay G D and Woolard R H,“Randomized, prospective trial of bilevel versus continuous positive airway pressure in acute
pulmonary edema”, Crit. Care Med. (1997), Apr; 25 (4): pp. 620–628.
19. Parmley W W, “Pathophysiology and current therapy of congestive heart failure”, J. Am. Coll. Cardiol. (1989), 13(4): pp.
771–785.
20. Maisel A S, Krishnaswamy P, Nowak R M et al.,“Rapid measurement of B-type natriuretic peptide in the emergency diagnosis
of heart failure”, N. Engl. J. Med. (2002), 347: pp. 161–167.
21. Mueller C, Scholer A, Laule-Kilian K, et al., “Use of B-type natriuretic peptide in the evaluation and management of acute
dyspnea”, N. Engl. J. Med. (2004), 350; pp. 647–654.
22. McCullough P A, Nowak R M, McCord J, et al., “B-type natriuretic peptide and clinical judgment in emergency diagnosis of
heart failure: analysis from Breathing Not Properly (BNP) Multinational Study”, Circulation (2002), 106: pp. 416–422.
23. Wright S P, Doughty R N, Pearl A et al., “Plasma amino-terminal pro-brain natriuretic peptide and accuracy of heart-failure
diagnosis in primary care: a randomized, controlled trial”, J. Am. Coll. Cardiol. (2003), 42: pp. 1,793–1,800.
24. Peacock, et al., “Prospective randomized outcomes study of acutely decompensated CHF treated initially in outpatients with
Natrecor (PROACTION)”, J. Am. Coll. Cardiol. (2003), 4 (Suppl A): 336A, CHF and Pulmonary Edema.
6
BUSINESS BRIEFING: US CARDIOLOGY 2004