Transcript Heart Failure PHCL

Heart Failure
Dr. Emtenan AlHarbi
Clinical pharmacy department
Learning objectives
 Differentiate between the common underlying etiologies of
heart failure, including ischemic, non-ischemic, and
idiopathic causes.
 Describe the pathophysiology of heart failure as it relates to
neurohormonal activation and the sympathetic nervous
system
 Identify signs and symptoms of heart failure and classify a
given patient by New York Heart Association Functional
classification and ACC/AHA heart failure staging.
Learning objectives
 the goals of therapy for a patient with heart failure.
 Non-pharmacological treatment plan which includes patient
education for managing heart failure.
 Develop a specific evidence-based pharmacological treatment
plan for a patient with heart failure based on disease severity
and symptoms.
Definition of HF
 HF is a complex clinical syndrome that results from any
structural or functional impairment of ventricular filling or
ejection of blood.
 The cardinal manifestations of HF are dyspnea and fatigue,
which may limit exercise tolerance, and fluid retention,
which may lead to pulmonary and/or splanchnic congestion
and/or peripheral edema.
Epidemiology
 Heart failure manifest most commonly in adults over the age
of 60.
 The growing prevalence of HF!
 Men> women.
Classifications of HF
Primary underlying etiology as ischemic or nonischemic.
2. Main component of the cardiac cycle leading to
impaired ventricular function. ( systolic or diastolic )
3. Ventricular dysfunction can also involve either the left or
right side or both.
1.
Hypertension
EF normal or increased
EF < 40% , Usually
from CAD
Pathophysiology
3D Medical Animation Congestive Heart Failure
Animation.
Physiology
Autonomic nervous
system, where sympathetic
stimulation of B
adrenergic receptors
CO=
CO=
HR
70ml\min
1. Preload (venous return)
2. Afterload (systemic pressure)
3. Contractility (inotropic state)
*
*
SV
72 beat/min
CO=5040 ml\min ~5L\min
Pathophysiology
 Compensatory mechanisms:
Preload and Frank-Starling mechanism.
2. Tachycardia and increased afterload.
3. Cardiac hypertrophy and remodeling.
1.
Pathophysiology
Neurohormonal pathways (RAAS + SNS)
Angiotensin II
Potent VC ↑SVR↑ BP↑afterload ↓SV ↓CO,
it also reduces hypertrophy and the release of
aldosterone, NE, ET1 and vasopressin
Aldosterone
Na+ -water retention ↑ preload and CO, it also cause
electrolyte disturbance  arrhythmia
↑HR and CO by sympathetic activation  arrhythmia,
ischemia, cell death.
NE
Endothelin
Potent VC
Arginine
vasopressin
Water retention (dilutional hyponatremia) and VC
Pathophysiology
Counter regulatory hormones
Natriuretic Peptides (ANP, ↓Na absorption from
BNP)
kidney and cause VD
by cGMP.
Bradykinin
VD peptide
Nitric oxide
VD and antagonize ET1
Framingham Criteria for Diagnosis of Congestive Heart Failure
The concurrent presence of two major criteria or one major and two minor criteria were required for the clinical
diagnosis of congestive heart failure
Minor criteria were acceptable only if not attributable to another medical condition.
Major
criteria
Paroxysmal nocturnal dyspnea
Orthopnea
Elevated jugular venous pulse/pressure
Positive hepatojugular reflux (later renamed abdominojugular test)
HF treatment (diuretic)-related 4.5 kg or greater weight loss in 5 days
Rales
Cardiomegaly (standing PA chest x-ray)
Pulmonary edema (chest x-ray)
S3 gallop
Minor
criteria
Bilateral ankle (peripheral, dependent) edema
Night cough
Dyspnea on exertion/exercise
Hepatomegaly
Pleural effusion
Tachycardia (over 120 bpm)
Non-HF treatment-related 4.5 kg weight loss or more in 5 days
Precipitating and Exacerbating Factors in
HF
Negative Prognostic Factors
 Clinical
 Increased Age, Diabetes, Smoking
 Laboratory
 Hyponatremia, Elevated
neurohormones
 Electrophysiological
 A-fib, A-flutter, Ventricular ectopy, V-
tach
 Hemodynamic
 Reduced EF, Increased Pulm Cap
Wedge Pressure
Clinical presentation and diagnosis
 Patient history
 PMH,FH and SH.
 Medication HX
PND
Clinical presentation and diagnosis*
Diagnosis
 Signs:
 JVP and HJR watch this on
 Chest auscultation.
 Edema.
Edema
Diagnosis
 Laboratory tests.
 BNP.
 ECG.
 Scr\CBC.
 CXR.
 Echocardiogram. watch this on
Tests for Patients with Suspected Heart Failure
Test
Indications
Interpretation/considerations
12-lead ECG
Routine
HF unlikely if ECG completely normal; ECG may suggest the cause of HF
CBC
Routine
Anemia may cause, exacerbate, or mimic (eg, "high-output") HF
Urinalysis
Routine
Proteinuria indicates nephrotic syndrome or severe congestive HF; hematuria
and casts indicate glomerulonephritis
Serum electrolytes (including Mg, Ca)
Routine
Establish baseline before starting drug therapy (eg, exclude hyperkalemia)
Serum creatinine, BUN
Routine
Elevated in renal failure/dysfunction; has major implications for HF
management
Liver (function) tests
Routine
Elevated levels may reflect hepatic congestion or alcohol-related
cardiomyopathy; hypoalbuminemia may reflect protein losing enteropathy or
poor nutritional status
Blood glucose
Routine
Screen for diabetes
Blood lipid profile
Routine
Screen for dyslipidemia
TSH
Routine
Both hyperthyroidism and hypothyroidism can cause or contribute to HF
Serum ferritin level, transferrin saturation
Suspected hemochromatosis
Hemochromatosis-related LV dysfunction improves with phlebotomy/chelation
HIV screening test
High-risk factors
HF is usually a late manifestation of HIV infection
Spirometry, peak flow
Suspected pulmonary disease
Comorbid ischemic heart disease and COPD common
Chest radiograph
Routine
Cardiomegaly or pulmonary venous congestion suggests HF; may be first clue to
underlying cardiac or pulmonary disease
Echocardiography
Routine (if HF still suspected after
above studies)
Most practical test for identifying and quantitating LV dysfunction and valvular
lesions
Radionuclide ventriculography
Echocardiography findings
inconclusive
Provides highly accurate assessments of global and regional LV functions
Revascularization candidate with
angina
Concurrent angioplasty (+/- stents), if indicated
Laboratory
Radiologic/imaging
Invasive
Coronary angiography
Treatment of HF
 Desired therapeutic outcomes
 There is no cure for HF.
 The general management goals for chronic HF include
preventing the onset of clinical symptoms or reducing
symptoms.
2. preventing or reducing hospitalizations.
3. slowing progression of the disease
4. improving quality of life, and prolonging survival
1.
Treatment of HF
 Control and treatment of contributing disorder
Test for IHD.
Control RF.
Surgical repair if necessary.
Condition \medication that exacerbate HF.
Alcohol.
Treatment of HF
 Non-pharmacologic intervention
 Weight self monitoring .(when to seek medical attention)
 Adherence.( how to improve)
 Dietary modification. (fluid\salt)
 Exercise (when? what?).
 Smoking cessation.(40% mortality)
 Immunizations.
Treatment of HF
 Pharmacologic treatment
1.
2.
3.
4.
5.
6.
7.
8.
Diuretics.
ACE-inhibitor.
ARBs
Hydralazine\isosorbidedinitrate.
B-blocker.
Aldosterone antagonist.
Digoxin.
CCB.
Stage D
 Inotropes — Inotropic agents are used during acute exacerbations of heart
failure to improve cardiac output and to stabilize patients awaiting heart
transplantation. Their effect is mediated through higher intracellular cyclic
adenylate monophosphate (cAMP) levels, either by increased production
(catecholamines) or by decreased degradation (phosphodiesterase III
inhibition).
 Catecholamines — Sympathomimetic stimulation by catecholamine agents
improves myocardial contractility and may have an additional beneficial effect
on peripheral vascular beds .Dopamine is the preferred drug during
decompensated heart failure (usually in combination with intravenous
milrinone), although dobutamine has the additive effect of reducing afterload.
 Milrinone — Intravenous milrinone, a phosphodiesterase III inhibitor, is the
preferred drug in decompensated heart failure, as it increases contractility and
reduces afterload without a significant increase in myocardial oxygen
consumption.
Treatment of HF
 Diuretics
 Diuretics inhibit the reabsorption of sodium or chloride at
specific sites in the renal tubules.
 Loop diuretics have emerged as the preferred diuretic agents
for use in most patients with HF.
 Thiazide diuretics may be considered in hypertensive patients
with HF and mild fluid retention because they confer more
persistent antihypertensive effects.
Diuretics
 Diuretics act at the loop of Henle
 Loop diuretics: Bumetanide, furosemide, and torsemide
 Diuritic act in the distal portionof the tubule
 thiazides, metolazone, and potassiumsparing agents (e.g.,
spironolactone)
Treatment of HF
 Loop diuretics.
Practical Diuretic Use in Heart Failure
 Use diuretic cautiously in patients with
 poorly controlled diabetes
 symptomatic benign prostatic hypertrophy
 increased risk of volume depletion
 Review potential drug interactions (eg, thiazides markedly
increase serum lithium levels but furosemide appears to
have little effect)
 Treat diuretic refractory patients with both a thiazide and
loop diuretic; administer the thiazide 1 hr before the loop
diuretic and monitor closely for symptomatic hypotension
Practical Diuretic Use in Heart Failure
 Treat mild volume overload with a thiazide
(hydrochlorothiazide 25 mg/day)
 Treat moderate/severe volume overload, renal
insufficiency (CrCl [GFR] 15-30 mL/min/1.73 m2), or
thiazide-refractory edema with a loop diuretic (eg,
furosemide 20-40 mg/day).
 Titrate to desired effect.
 Titrate diuretic to achieve 0.5-1 kg weight loss daily until
euvolemic, then to maintain euvolemia; if furosemide
requirement is more than 160 mg furosemide, divide into 2
doses daily
Caution
 Diuretics can cause the depletion of potassium and
magnesium, which can predispose patients to serious cardiac
arrhythmias
 Excessive diuresis may result in prerenal azotemia,
hypokalemia, hypomagnesemia, inability to optimize ACEI
dose, and orthostatic hypotension.
Practical Diuretic Use in Heart Failure
 Monitor serum electrolytes (especially K and Mg), BUN,
and Cr closely until values are stable and whenever
medication dosages are increased
 Fluctuations in volume status may require frequent
diuretic dosage adjustments, which in turn requires close
monitoring for electrolyte imbalances and hypotension
 Lying supine for 1-2 hr after receiving a diuretic increases
its efficacy
Management of diuretic-related complications
 Hyponatremia: If volume overloaded, restrict fluid intake to 1 L
daily; if volume depleted, reduce diuretic dosage
 Hypokalemia (K less than 4 mEq/L): If persistent, consider adding
a K supplement or K-sparing diuretic (eg, amiloride 2.5 mg/day or
spironolactone 25 mg/day) to the ACEI and diuretic regimen;
recheck K and Cr levels in 5-7 days; then, slowly increase dose as
required. Check K and Cr 5-7 days after any dose change.
Management of diuretic-related complications
 Hyperkalemia (K more than 5.5 mEq/L): Assess and correct
potential causes (eg, K supplementation or K-sparing diuretic, ACEI
intolerance, renal insufficiency, or digoxin toxicity).
 Hypomagnesemia: Add oral Mg supplementation; correction
often facilitates correction of associated hypokalemia .
 Orthostatic hypotension: Absence of congestion and a raised
BUN-to-creatinine ratio (more than 20:1) suggests over-diuresis and
volume depletion; if not volume depleted, consider ACEI
intolerance.
Hydralazine and Nitrate
 Hydralazine and Nitrate (Hydranit and African american
population): it is to reduce cardiac preload and afterload by
achieving both venous and arterial vasodilation. Hydralazine
is an arterial vasodilator and nitrates are predominantly
venodilators.
 These effects can reduce intracardiac filling pressures which
may reduce adverse cardiac remodeling.
Digoxin
 Has a positive inotropic effect (mediated by Na+/K+ ATPase inhibition
and increase in intracellular Ca+). It is improved isolated myocyte
contractile performance (increased shortening velocity) and overall left
ventricular (LV) systolic function .
 Has a negative chronotropic effect, exerts an antiadrenergic action in
patients with heart failure (HF) by inhibiting sympathetic outflow and
augmenting parasympathetic tone.
 Digitalis can also be beneficial in patients with HF due to systolic
dysfunction with atrial fibrillation (AF) with rapid ventricular response.
 There is no evidence that digoxin improves survival in HF patients.
Aldosterone antagonists
 Decrease sodium reabsorption and potassium excretion in the




collecting ducts of kidneys.
Their potassium-sparing diuretic effect makes them particularly
suitable for use in conjunction with loop diuretics and thiazides.
Both spironolactone and eplerenone have been shown to reduce
mortality in adults with heart failure when added to standard
therapy .
This effect is independent of their diuretic effect and is mediated
by inhibition of myocardial fibrosis, an important component of
LV remodeling
Side effects include hyperkalemia (with both) and gynecomastia
(with spironolactone).
ACE inhibitor and ARBs
 ACE inhibitors (cornerstone) and ARBs inhibit the RAAS,
thereby decreasing afterload and improving cardiac output and,
on chronic use, by mediating reversal of LV remodeling.
 Side effects:
1. Hypotension.(diuretics)
2. Hyperkalemia.
3. Cough.
 ARBs: usually reserved for patients unable to tolerate ACE
inhibitors due to cough or angioedema.
Calcium channel blockers
 Amlodipine and felodipine (little or no negative inotropic
activity at the usual therapeutic doses) appear to be safe in
patients with HF and can be used if treatment with a calcium
channel blocker is necessary for another indication, such as
angina or hypertension.
BB
 Beta-blockers counteract the maladaptive effects of chronic
sympathic activation of the myocardium.
 In adults with heart failure, they improve patient survival,
reverse LV remodeling, reduce all-cause mortality and
decrease hospitalization in patients with HF and left
ventricular systolic dysfunction (LVEF ≤ 35 to 40 percent
and decrease myocardial fibrosis.
Relative contraindications of BB in patients
with HF include
●Heart rate <60 bpm
●Symptomatic hypotension
●Greater than minimal evidence of fluid retention
●Signs of peripheral hypoperfusion
●PR interval >0.24 sec
●Second- or third-degree atrioventricular block
●History of asthma or reactive airways
●Peripheral artery disease with resting limb ischemia
:
BB
 In the absence of a contraindication, our recommendation is
to offer carvedilol, metoprolol succinate, or bisoprolol to
patients with NYHA class II, III, or stable class IV HF with
left ventricular ejection fraction less than 40 percent
Treatment of HF
 HF with preserved LVEF.
 Also called diastolic dysfunction (EF 40-60%)
 Causes: HTN and DM.
 Better survival.
HFpEF
Outcome evaluation
 Major outcome parameters focus on:
(1) volume status (diuretics)
(2) exercise tolerance.
(3) overall symptoms/quality of life.
(4) adverse drug reactions.
(5) disease progression and cardiac function (echo Q 6 Months)
Heart Failure
References
 VardenyO,M.H.Ng .T(2010).Heart failure.in M
chisholm,Tschwinghammer,BWells,PMalone,JKolesar.JDipiro.
Pharmacotherapy principles and practice (2ed).McGraw
Hill companies,Inc.
 2013 ACCF/AHA Heart Failure Guideline: Full Text.Yancy et al.
JACC Vol. 62, No. 16, 2013