B. A.

Afrane
 HF – complex clinical syndrome results in any
structural or functional cardiac disorder
 Impairs ability of the ventricle to fill with or
eject blood
 Subdivided into HF with reduced LVEF or HF
with preserved LVEF (HFPEF, formerly-
diastolic dysfunction)
 Symptoms
◦ Limitation in activity using NYHA functional
classification system and ACC-AHA classification of
CHF
◦ Cardinal signs and symptoms (peripheral edema,
dyspnea, fatigue) of HF must be elevated in light of
patient’s medical hx, physical exam and results of
additional testing
 Co-existing med conditions leading to HF
◦ Ischemic heart disease, hypertension, A-Fib, DM,
sleep apnea
 Conditions that results from HF
◦ A-Fib, cachexia, depression
 Will influence overall prognosis and treatment
therefore should be assessed routinely
 Several classes of meds (NSAIDS, glitazones)
may exert unfavorable hemodynamics and
ppt HF symptoms in pts with previously
compensated HF
 Anthracycline and cancer chemotherapeutic
drugs are cardiotoxic and can cause HF
 Treatment goals
◦ Improve symptoms
◦ Decrease hospitalizations
◦ Prevent premature death
 Treatment cornerstone for HF with reduced
◦ Optimize life-prolonging therapies
 ACEI, ARB, β-blockers, aldosterone antagonists
◦ Promote healthy lifestyle choices
 Sodium restriction , exercise training
 Management of acute decompensated HF
◦ Prompt recognition of symptoms and appropriate tx
critical
◦ Volume overloaded pts
 IV loop diuretics
 Inotropes (failed to show long-term benefit in clinical
trials)
 Implantable cardioverter-defribrillator
reduces the risk of sudden death in pts with
reduced LVF
 Cardiac resynchronization therapy can be
used in combination to improve symptoms
and QOL in pts with severe HF symptoms
 Clinical evidence lacking on optimal tx in
HFPEF
 Although controversial, certain pts may
respond differently to drug therapy (African
American pts, women).
 HF is an extreme serious condition and
requires careful diagnosis, ongoing
monitoring, and the implementation of
evidence-based therapy.
 Herbal remedies (e.g. hawthorn) have some
evidence to support their role in improving
symptoms of HF though evidence
demonstrating improvement in mortality is
lacking.
 Herbals can also potentially interact with
other heart medications
 CHF – subset of HF characterized by LV
systolic dysfunction and volume excess
presenting as an enlarged, blood-congested
heart.
 Some patients may not have symptoms of
congestion but reduced CO (fatigue and
reduced exercise).
 Revised guidelines from Heart Failure Society
of American Society, ACC, AHA, ESC
 Revised guidelines 2009 AHA/ACC
◦ Four stages of HF
 ACC/AHA: 1995, 2001, 2005, 2009
my.americanheart.org
 High Risk – HTN, CAD, DM, Family Hx of
cardiomyopathy
 Asymptomatic LVD- previous MI, LV systolic
dysfunction, asymptomatic valvular disease
– NYHA I
 Symptomatic HF- known structural heart disease,
SOB and fatigue, reduced exercise tolerance,
symptomatic with moderate exertion – NYHA II
 Symptomatic HF- known structural heart disease,
SOB and fatigue, reduced exercise tolerance –
symptomatic with minimum exertion – NYHA III
 Refractory End-Stage HF: Marked symptoms at rest
despite maximal medical therapy – NYHA IV
Hunt SA et al. ACC/AHA Guidelines 2005 & 2001; Circulation 2001;104:2996.
Farrell MH, Foody JM, Krumholz HM. JAMA 2002;287:890
  HF affects 5.7 Million: 3.1 M men, 2.6 M
women (self-report, age ≥20yo, NHANES-2008)
 Lifetime risk 20% (≥40yo, Framingham[FHS])
 Hospitalizations > 1 M / year
 Prevalence and Incidence of HF increases
with age
◦ 670,000 new cases age ≥45yo (FHS)
◦ 56,000 deaths; 1 in 9 deaths (NCHS)
 ≥50% diagnosed w/ HF die within 5 yrs
(Olmsted)

Roger V et al. Heart Disease and Stroke Statistics—2011 Update. Circulation 2011;123(4):e18-e209.
 Olmstead County: N=4537 HF patients
(1979-2000) by ICD-9-CM codes (98% (+) Framingham
criteria)

MEN WOMEN

Rogers VL et al, JAMA 2004;292:344

Aurigemma GP, Gaasch WH. NEJM 2004;351:1097-105.
4596 HF patients, Mayo Clinic

Owan TE et al, NEJM 2006; 355(3):254

 X.Y., a 60-y-old man is admitted with a chief
complaint of increasing shortness of breath (SOB) and
8-kg weight gain. Two weeks before admission, he
noted the onset dyspnea on exertion (DOE) after one
flight of stairs, orthopnea and ankle edema. Since
then, his symptoms have worsened. He has noted
episodic bouts of paroxysmal nocturnal dyspnea
(PND), and has been able to sleep only in a sitting
position. XY reports a productive cough, nocturia (2
to 3X/night) and edema.
 XY’s other medical problems include long hx of
heartburns, a 10 yr hx of osteoarthritis, depression
and HTN, which has been poorly controlled. A strong
family hx of DM is also present
 Physical examination reveals dyspnea, cyanosis,
and tachycardia. XY’s vital signs are: BP, 160/100
mm Hg; pulse 90 b/m; and RR 28 bpm. He is 5’
11” and weighs 78 kg. His neck veins are
distended. On cardiac exam, an S3 gallop is
heard; the point of maximal impulse is at the 6 th
intercostal, 12cm from the midsternal line. His
liver is enlarged and tender to palpation, a
positive hepatojugular reflux is observed. He is
noted to have 3+ pitting edema of the
extremeties and sacral edema. Chest exam
reveals inspiration rales and rhonchi bilaterally.
 The medication Hx reveals the ff current meds:
HCTZ 25 mg QD, ibuprofen 600 mg QID,
ranitidine 150 mg QHS, citalopram 20 mg QD. He
has no allergies and no dietary restrictions.
 Admitting lab values are: Hct 41.1%, WBC
5,300/L, Na 132 mEq/L, K 3.2mEq/L, Cl 100
mEq/L, HCO3 30 mEq/L, Mg 1.5 mEq/L, FBS 100
mg/dL, UA 8 mg/dL, BUN 40 mg/dL, SCr 0.8
mg/dL, ALP 44 units/L, AST 30 units/L, BNP 364
pg/mL, (nl  200 pg/mL), TSH 2.0 units/mL
 CXR shows bilateral pleural effusions and
cardiomegaly. What signs, symptoms and lab
abnormalities of HF does XY exhibit? Relate
these clinical findings to the pathogenesis of
the disease and to left-sided or right-sided
HF
 Subjective  Subjective
◦ DOE
◦ SOB
◦ Orthopnea (2 to 3 pillows)
◦ PND, cough
◦ Weakness, fatigue, confusion ◦ Peripheral edema
◦ Weakness, fatigue
 Objective  Objective
◦ LVH
◦ BP ◦ Weight gain (fluid
◦ EF  40% retention)
◦ Rales, S3 gallop rhythm ◦ Neck veins distention
◦ Reflex tachycardia
◦ BUN (poor renal perfusion) ◦ Hepatomegaly
◦ Hepatojugular reflux

Left Ventricular Failure Right Ventricular Failure

 LHF
◦ Wt gain and edema ⇒ Na and water retention ⇒d/t  renal perfusion
◦ As RBF and decrease, a disproportionate amt of BUN is retained
◦ Prerenal azotemia ⇒BUN/SCr > 20:1
◦ What is XY’s?
◦ What could be other causes of prerenal azotemia in XY’s case?
 RHF
◦ Hypervolemia, valvular disease or pulmonary HTN i.e. overall elevation of
CVP
◦ Redistribution of fluid into interstitial spaces. Ankle and pretibial edema,
localization of fluid in dependent portions of body secondary to
gravitational forces
◦ Hepatomegaly, hepatic tenderness, ascites d/t venous congestion and
increased portal vein pressure.
◦ Metabolism of drugs dependent on liver for elimination can be impaired
b/o retrograde venous congestion and decreased arterial perfusion of the
liver
◦ Congestion of GIT makes pt anorectic
Systolic dysfunction
EF
Diastolic dysfunction
Pathophysiology
Activation of SNS
RAAS
Endothelins
Natriuretic peptides
vasopressin receptor antagonists
calcium sensitizers
inflammatory cytokines, interleukins, tissue necrosis factor,
prostacyclin and nitric oxide
Cardiac remodeling
Cardiac dilatation
Frank-Starling curve
Cardiac hypertrophy
 Physical activity
 Na-restricted diet
 Diuretics
 Aldosterone antagonists
 ACEI and ARB
 Β-adrenergic Blocking Agents
 Digitalis glycosides (digoxin)
 Other vasodilating drugs (hydralazine and nitrates)
 Other Inotropic agents (D and D, milrinone?)
 Calcium channel blockers
 Implantable cardioverter-defibrillator
 Cardiac synchronization
 Left ventricular assist devices
 New Idiopathic DCM dx = Familial in 20-
35% (when 1st degree family members
screened)
 Point mutations in 31 autosomal and 2
X-linked genes
◦ But only account only for 30-35% genetic
causes

Hershberger RE, Siegfried JD, JACC 2011;57(16):1641-9

 Affect sxs, Rx, prognosis
 Cardiovascular
◦ CHD & CHD risk factors: HTN, DM, metabolic
syndrome, obesity
◦ Valvular disease
◦ Arrhythmias
◦ Other atherosclerotic disease: PAD, stroke
 Noncardiac comorbidities
◦ Too many to list… but will highlight:
 Anemia
 Sleep apnea
 ~25% in HF population
◦ Etiology: hemodilution, Fe or Epo deficiency, CKD
 1-g/dL Hgb reduction associated with a 20%
increase in risk of death
Tang WH et al, JACC 2008;51:569-576; Anand I et al, Circulation 2004;110:149-154

 Treatment is relatively easy

◦ Iron supplementation
◦ IV iron (short-term)
◦ Erythropoiesis-stimulating agents (short term)
  Similar sxs as HF
 Common (12-53%) but under-diagnosed
 Thus undertreated

Mild to No OSA

Untreated OSA

Wang H et al, JACC 2007;49(15):1625-31. Kasai T, Bradley TD, JACC 2011;57(2):119-27 [REVIEW]
 Guidelines
◦ ACC/AHA: 1995, 2001, 2005, 2009
◦ HFSA: 1999, 2006, 2010
 Medications
◦ Diuretics, ACE inhibitors* &/or Angiotensin receptor blockers*
&/ or Hydralazine/Nitrates*, Beta-blockers*, Aldosterone
antagonists*, Digoxin
 Electrophysiology (EP) Devices
◦ Implantable cardioverter defibrillator (ICD)
◦ Biventricular pacemaker (CRT)
 Surgery
◦ Revascularization
◦ Ventricular restoration (Dor procedure)
◦ Mitral valve surgery
◦ Cardiac transplantation
◦ Mechanical circulatory support (VAD)
 Stem cells?
Hemofiltration?

ARB, H/I in some. ICD

all

Jessup M, Brozena S. NEJM 2003;348:2007

 , B-blockers

Kittleson MM, Kobashigawa JA, Circulation 2011;123:1569-1574

 Identify and avoid exacerbating factors for HF
 Behavioral management
◦ Fluid restriction (2 L = ½ gallon)
◦ Salt restriction (2 g)
◦ Daily weights (?sliding scale diuretics for the savy)
◦ Exercise
◦ Medical adherence
◦ No smoking
 Biomarkers: BNP/NT-proBNP
a.k.a. HF Core Measures
◦ New ones but not commonly available (ST2, endoglin, galectin-
3, cystatin C, neutrophil gelatinase-associated lipocalin, midregional pro-
adrenomedullin, chromogranin A, adiponectin, resistin, leptin)
 “Baseline/dry” weights & NTproBNP helpful
 Begin with ACC/AHA Stage A
 Optimize for Stages B-D
 Lots of meds with good data, but
challenges of polypharmacy
◦ Compliance, cost, HF severity
 Priorities
◦ B-blocker, ACE-I for all (aim for target doses)
◦ ARB as ACE-I alternative or if congested/
hypertensive
◦ Hydralazine/nitrate if African-American or
congested/hypertensive
◦ Diuretic PRN and/or Aldosterone blocker
◦ Digoxin if recurrent hospitalization
 Enalapril (Vasotec) 10 mg bid
ACE-I Captopril (Capoten) 50 mg tid*
Ramipril (Altace) 5 mg bid
Lisinopril (Prinivil, Zestril) 20 mg qd
Trandolapril (Mavik) 4 mg qd
Quinapril (Accupril) 20-40 mg bid

Bisoprolol (Zebeta) 10 mg qd
BB Carvedilol (Coreg) 25-50 mg bid **
Metoprolol XL/CR (Toprol XL) 200 mg qd
Metoprolol (Lopressor) 100 mg bid ‡
Atenolol (Tenormin) 100 mg qd ‡
*affected by food, ** depends on weight
no mortality data, ‡ not in guideline
 IV diuretics
◦ Bolus or continuous
 IV vasodilators
◦ Nitroglycerin, Nesiritide, Nitroprusside
 IV inotropes
◦ Milrinone, Dobutamine, Dopamine
 Optimize PO regimen
Advanced,
End-stage
Systolic HF
Hunt SA, et al. ACC/AHA HF Guidelines Update. Circulation 2009;119(14):e391-479.
 Ultrafiltration (aquapheresis therapy):
◦ Peripheral or central venous access, ≤4 L off
in ≤8 hrs, max removal rate 500 mL/hour
◦ UNLOAD trial: n=200, RCT, UF vs IV diuretics
 At 48 hrs, UF group had 38%  weight loss, 28% 
net fluid loss
 At 90 days after hospital d/c, UF had  HF re-
hospitalizations,  ED or clinic visits
Costanzo MR et al. JACC 2007;49(6):675-83
 EECP (enhanced external
counterpulsation)
◦ Already used for angina pts
◦ PEECH trial: n=187, RCT, EECP vs usual care
 EECP pts had  exercise time, QOL, NYHA Class, but
no difference in peak VO2 changes
Feldman AM et al. JACC 2006;48(6):1198-205
  2° Prevention
◦ AVID (1997)
 1° Prevention
◦ MADIT (1996)
◦ MUSTT (1999) (EF 35-40%, +EPS)
◦ MADIT II (2002)
◦ SCD-HeFT (2004)

ACC/AHA/ESC guidelines
• Class I: LVEF ≤ 35%, NYHA II-III,
ICM LVEF ≤ 30%, NYHA I
• Class II: NICM LVEF ≤ 30% NYHA I
 40+ days post-MI/revascularization
 >3 months for NICM on optimal therapy
 Life expectancy >1 year
 Still, low referral rate
◦ 42% (LVEF≤35%) & 49% (LVEF≤30%) eligible pts
were referred (1 center, 2002-2006)

◦ Why? NNT = 6 (MADIT-II) to 14 (SCD-HeFT)

Bradfield J et al, PACE 2009; 32:S194–S197
 Patient vs Doctor?
 30% with chronic HF have
Ventricular Dyssynchrony
 CRT with biventricular pacemakers can
improve symptoms & survival*:
NYHA Class III-IV, LVEF <35%, basal QRS duration of
>120 msec

– MUSTIC (QRS >150 ms) (2001)

– MIRACLE (QRS >130 ms) (2002)
– COMPANION (QRS >120 ms) (2004)
– CARE-HF (QRS >120 ms) (2005)*
 After medical therapy optimized
 CRT has been mostly studied in the NYHA
III-IV population
◦ If CRT, HF = “Advanced”
 Consider CRT earlier? (earlier than NYHA
Class III)
◦ REVERSE Trial (2008)
◦ MADIT-CRT Trial (2009)
◦ RAFT Trial (2010)
• The only “cure”
• >89,000 Heart Tx worldwide, >50,000 in US
(1988-)

Hunt SA, Haddad F, JACC 2008:52:587-98. Hunt SA. NEJM 2006;355:3

 Mechanical Circulatory Support:
Ventricular Assist Devices: Bridge to Tx, Destination
Therapy
 Volume
Displacement
◦ Thoratec
◦ Novacor
◦ Heartmate LVAS
◦ Abiomed
 Axial Flow
◦ Heartmate II
◦ Jarvik
 Centrifugal
◦ CentriMag
◦ Heartware
Baughman KL, Jarcho JA. NEJM 2007;379(9):846-9.
 Q. Does XY have LSVD?
 s/s of XY
◦ SOB, crackles on auscultation, neck vein distention, edema all
limited in evaluating structural abnormalities
◦ Reduced exercise tolerance?
◦ Enlarged heart on CXR –suspicion of LVSD
◦ EF measurement differentiates between HF with LVSD and
HFPEF.ECHO measures ventricular wall thickness, chambers size,
valvular functioning, and pericardial thickness.
◦ EF estimates based on changes in ventricular chamber size
between diastole and systole. Not most accurate but comfortable.
◦ Radionuclide left ventriculography (same as multiple gated
acquisition scan) use radiolabel technetium as a tracer to measure
LV hemodynamics. Fails to give info about architecture of the LV.
◦ MRI and CT Scan good for ventricular mass evaluation not EF
◦ XY EF 30% -40% . XY shows combination of systolic and classic
congestive signs.
 Q. What stage of HF does XY exhibit
according to ACC/AHA criteria? How severe is
XY’s disability according to the NYHA fx class
of HF.
 ACC/AHA stage C – active symptoms of HF
and changes in cardiac structure
 NYHA fx class III – need to sleep upright,
inability to do even minimal physical activity.
 Q. What factors contributed to the cause of XY’s HF?
 Generally
◦ Age, HTN, MI, diabetes, tachycardia-induced
cardiomyopathy, valvular heart disease and obesity,
smoking, excessive EtOH, dyslipidemia, anemia, and CKD.
Also biochemical and genetic markers have been associated
with HF. CAD (MI) significant. 70% increase in HF after MI.
◦ With XY
 Poorly controlled BP – increase afterload on LV
 Like MI, HTN – myocyte hypertrophy, neurohormonal activation
leads to LVH. LVH assoc increased HF esp in the young. At BP
160/90 life risk of HF double that at 140/80
 Combined presence of HTN and HF assoc with worse outcome.
5-year mortality for men 76% and 69% for women.
 Reducing BP aggressively reduces mortality rate by 50%
 Q.
◦ Other with XY
 NSAIDS contribute to Na loading. Including cycloxygenase-2
inhibitors – renally mediated Na retention increasing blood
volume by about 50%.
 NSAIDS exacerbate HF symptoms and increase
hospitalizations for HF.
 Recent 2 cohort studies show dose related increase in risk of
death and hospitalizations for MI and HF with cox-2 and
some cox-1 (plus naproxen)
 Also note that blocking prostaglandins (prostacyclin and
thromboxane) leads to Na reabsorption and counteracting
beneficial effects of diuretics and ACEI
 AHA- Avoid NSAIDS in HF!!!
 8kg gain – fluid overload – replace HTCZ with loop diuretic
 ACEI must be added, beta-blocker when euvolumic, DC or
taper all NSAIDS, sub with acetaminophen
 Q. what are the therapeutic goals in treating
X.Y.?
◦ Provide symptomatic relief
 Reduction in pt’s complaints of SOB and PND, improve
sleep quality, exercise tolerance
◦ Weeks, get pt back to baseline parameters
 Reduced peripheral , sacral edema, weight loss,
slowing of HR to <90, nl BP, reduced BUN, smaller
heart size on CXR, decreased neck vein distention and
loss of S3 heart sound
◦ Long-term goal, improve EF, QAL, fewer
hospitalizations, avoid ADR with meds, increase
survival time.
 Q. Bed rest and a 3-g Na diet was ordered. The team
decides to initiate furosemide for XY. What is the
rationale for using diuretic and what route, dose, and
dosing schedule should be used?
 Diuretics produce symptomatic improvement more
than other drug for HF
◦ Relieves pulmonary and peripheral edema within hours or
days
◦ But can not maintain clinical stability for long and should
not be used alone
◦ Can activate RAAS and SNS (  bld volume) and lead to HF
progression
◦ Can be used acutely or chronically if clinical volume
overload is present
◦ Can be used intermittently titrated based on weight gain,
neck vein distension, peripheral edema or SOB
◦ Pt may be asked to take med when pt gains 1 lb in
a day or 5 lb in a week or have leg or abdominal
swelling.
◦ Can cause volume depletion, electrolyte
abnormalities, and diminished CO
◦ D/C in worsening RF or hypotension
◦ Torsemide more favorable than furosemide - 1 yr
open label of 234 pts only 17% of torsemide pts
likely to be admitted for HF vrs 32% furosemide pts.
Admission for all CV causes was 44% for torsemide
vrs 59% for furosemide
 Risk of arrhythmias increases by 27% for
every 0.5 mEq/L decrease in serum K below
3.0 mEq/L