Presentaci

1
(No Transcript)
2

• Low-Output Heart Failure
• Systolic Heart Failure (HFREF)
• Decreased Left ventricular ejection fraction
• Diastolic Heart Failure (HFPEF)
• Elevated Left and Right ventricular
  end-diastolic pressures
• Normal LVEF
• High-Output Heart Failure
• Seen with peripheral shunting, low-systemic
  vascular resistance, hyperthryoidism, beri-beri,
  carcinoid, anemia
• Often have normal cardiac output
• Right-Ventricular Failure
• Seen with pulmonary hypertension, large RV
  infarctions.

3
Causes of Low-Output Heart Failure

• Systolic Dysfunction
• Coronary Artery Disease
• Idiopathic dilated cardiomyopathy (DCM)
• 50 idiopathic (at least 25 familial)
• 9 myocarditis (viral)
• tachycardia, peripartum, hypertension, HIV,
  connective tissue disease, substance abuse
  (alcohol), doxorubicin/herceptin
• Hypertension
• Valvular Heart Disease
• Diastolic Dysfunction
• Hypertension
• Coronary artery disease
• Hypertrophic obstructive cardiomyopathy (HCM)
• Restrictive cardiomyopathy

4
(Mal)adaptation-hemodynamic
5
(Mal) adaptation-neurohormonal

• Activation of the sympathetic nervous system
• Vasoconstriction/increased afterload
• Tolerance
• Arhythmogenic

6

• Activation of renin-angiotensin system
• Na resorption
• Vasoconstriction
• Apoptosis/fibrosis

7

• Antidiuretic hormone
• Proinflammatory cytokines
• TNFalpha
• IL-6

8
Clinical Presentation of Heart Failure

• Due to excess fluid accumulation
• Dyspnea (most sensitive symptom)
• Edema
• Hepatic congestion
• Ascites
• Orthopnea, Paroxysmal Nocturnal Dyspnea (PND)
• Due to reduction in cardiac ouput
• Fatigue (especially with exertion)
• Weakness

9

• S3 gallop
• Low sensitivity, but highly specific
• Cool, pale, cyanotic extremities
• Have sinus tachycardia, diaphoresis and
  peripheral vasoconstriction
• Crackles or decreased breath sounds at bases
  (effusions) on lung exam
• Elevated jugular venous pressure
• Lower extremity edema
• Ascites
• Hepatomegaly
• Splenomegaly
• Displaced PMI
• Apical impulse that is laterally displaced past
  the midclavicular line is usually indicative of
  left ventricular enlargementgt

10
Lab Analysis in Heart Failure

• CBC
• Since anemia can exacerbate heart failure
• Serum electrolytes and creatinine
• before starting high dose diuretics
• Fasting Blood glucose
• To evaluate for possible diabetes mellitus
• Thyroid function tests
• Since thyrotoxicosis can result in A. Fib,
• and hypothyroidism can results in HF.
• Iron studies
• To screen for hereditary hemochromatosis as cause
  of heart failure.
• ANA
• To evaluate for possible lupus
• Viral studies
• If viral mycocarditis suspected

11
Laboratory Analysis (cont.)

• BNP
• With chronic heart failure, atrial mycotes
  secrete increase amounts of atrial natriuretic
  peptide (ANP) and brain natriuretic pepetide
  (BNP) in response to high atrial and ventricular
  filling pressures
• Usually is gt 400 pg/mL in patients with dyspnea
  due to heart failure.

12
Chest X-ray in Heart Failure

• Cardiomegaly
• Cephalization of the pulmonary vessels
• Kerley B-lines
• Pleural effusions

13
Cardiomegaly
14
Pulmonary Edema due to Heart Failure
15
Kerley B lines
16
Cardiac Testing in Heart Failure

• Electrocardiogram
• May show specific cause of heart failure
• Ischemic heart disease
• Dilated cardiomyopathy first degree AV block,
  LBBB, Left anterior fascicular block
• Amyloidosis pseudo-infarction pattern
• Idiopathic dilated cardiomyopathy LVH
• Echocardiogram
• Left ventricular ejection fraction
• Structural/valvular abnormalities

17
Further Cardiac Testing in Heart Failure

• Coronary arteriography
• Should be performed in patients presenting with
  heart failure who have angina or significant
  ischemia
• Reasonable in patients who have chest pain that
  may or may not be cardiac in origin, in whom
  cardiac anatomy is not known, and in patients
  with known or suspected coronary artery disease
  who do not have angina.
• Measure cardiac output, degree of left
  ventricular dysfunction, and left ventricular
  end-diastolic pressure.

18
Further testing in Heart Failure

• Endomyocardial biopsy
• Not frequently used
• Amyloidosis, giant-cell myocarditis

19
Classification of Heart Failure
ACCF/AHA Stages of HF ACCF/AHA Stages of HF NYHA Functional Classification NYHA Functional Classification
A At high risk for HF but without structural heart disease or symptoms of HF. None  
B Structural heart disease but without signs or symptoms of HF. I No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF.
C Structural heart disease with prior or current symptoms of HF. I No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF.
C Structural heart disease with prior or current symptoms of HF. II Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in symptoms of HF.
C Structural heart disease with prior or current symptoms of HF. III Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes symptoms of HF.
C Structural heart disease with prior or current symptoms of HF. IV Unable to carry on any physical activity without symptoms of HF, or symptoms of HF at rest.
D Refractory HF requiring specialized interventions. IV Unable to carry on any physical activity without symptoms of HF, or symptoms of HF at rest.
20
Aggravating Factors

• Medications
• New heart disease
• Myocardial ischemia

• Endocarditis
• Obesity
• Hypertension
• Physical activity
• Dietary excess

• Pregnancy
• Arrhythmias (AF)
• Infections
• Thromboembolism
• Hyper/hypothyroidism

21

• Heart Failure and Myocardial Ischemia
• Coronary HD is the cause of 2/3 of HF
• Segmental wall motion abnormalities are not
  specific if ischemia
• Angina coronary angio and revascularization
• No angina
• Search for ischemia and viability in all ?
• Coronary angiography in all ?

22

ACE-i. Mechanism of Action
VASOCONSTRICTION
VASODILATATION
ALDOSTERONE
PROSTAGLANDINS
VASOPRESSIN
tPA
Kininogen
SYMPATHETIC
Kallikrein
Angiotensinogen
RENIN
BRADYKININ
Angiotensin I
A.C.E.
Kininase II
Inhibitor
ANGIOTENSIN II
Inactive Fragments
23
ACE-I. Clinical Effects

• Improve symptoms
• Reduce remodelling / progression
• Reduce hospitalization
• Improve survival

24
Mortality Reduction with ACE-i
Study ACE-i Clinical Seting CONSENSUS Enalapril CH
F SOLVD treatment Enalapril CHF AIRE Ramipril CHF
Vheft-II Enalapril CHF TRACE Trandolapril CHF /
LVD SAVE Captopril LVD SMILE Zofenopril High
risk HOPE Ramipril High risk
25
ACE-i
0.8
0.7
Placebo
0.6
Probabiilityof Death
plt 0.001
0.5
0.4
plt 0.002
0.3
Enalapril
0.2
0.1
0
0
12
11
10
9
8
7
6
5
4
3
2
1
CONSENSUS N Engl J Med 19873161429
Months
26
ACE-i
30
Asymptomatic ventricular dysfunction post MI
Placebo
n1116
20
Mortality,
Captopril
n1115
10
n 2231 3 - 16 days post AMI EF lt 40 12.5 ---
150 mg / day
² -19
p0.019
0
SAVE N Engl J Med 1992327669
4
3
0
1
2
Years
27
ACE-i. Indications

• Symptomatic heart failure
• Asymptomatic ventricular dysfunction
• - LVEF lt 35 - 40
• Selected high risk subgroups

AHA / ACC HF guidelines 2001 ESC HF guidelines
2001
28

• ACE-i. Practical Use
• Start with very low dose
• Increase dose if well tolerated
• Renal function serum K after 1-2 w
• Avoid fluid retention / hypovolemia (diuretic
  use)
• Dose NOT determined by symptoms

29
ACE-i. Dose (mg) Initial Maximum Captopril
6.25 / 8h 50 / 8h Enalapril 2.5 / 12 h 10 to
20 / 12h Fosinopril 5 to 10 / day 40 /
day Lisinopril 2.5 to 5.0 / day 20 to 40 /
day Quinapril 10 / 12 h 40 / 12 h Ramipril 1.25
to 2.5 / day 10 / day
AHA / ACC HF guidelines 2001
30

• ACE-I. Adverse Effects
• Hypotension (1st dose effect)
• Worsening renal function
• Hyperkalemia
• Cough
• Angioedema
• Rash, ageusia, neutropenia,

31

• ACE-I. Contraindications
• Intolerance (angioedema, anuric renal fail.)
• Bilateral renal artery stenosis
• Pregnancy
• Renal insufficiency (creatinine gt 3 mg/dl)
• Hyperkalemia (gt 5,5 mmol/l)
• Severe hypotension

32
ß-Adrenergic Blockers Mechanism of action

• Density of ß1 receptors
• Inhibit cardiotoxicity of catecholamines
• Neurohormonal activation
• HR
• Antiischemic
• Antihypertensive
• Antiarrhythmic
• Antioxidant, Antiproliferative

33
ß-Adrenergic Blockers
100
90
80
Survival
Carvedilol
70
p0.00014 35 RR
60
Placebo
N 2289 III-IV NYHA
50
24
0
20
16
12
8
4
28
Months
COPERNICUS NEJM 20013441651
34
ß-Adrenergic Blockers When to start

• Patient stable
• No physical evidence of fluid retention
• No need for i.v. inotropic drugs
• No contraindications
• In hospital or not

35
ß-Adrenergic Blockers Dose (mg)
Initial Target Bisoprolol 1.25 / 24h 10 /
24h Carvedilol 3.125 / 12h 25 / 12h Metoprolol
succinnate 12,5-25 / 24h 200 / 24h

• Start Low, Increase Slowly
• Increase the dose every 2 - 4 weeks

36
ß-Adrenergic Blockers Adverse Effects

• Hypotension
• Fluid retention / worsening heart failure
• Fatigue
• Bradycardia / heart block

37

Aldosterone Inhibitors
ALDOSTERONE
Spironolactone
-
Competitive antagonist of the aldosterone
receptor (myocardium, arterial walls, kidney)

• Retention Na
• Retention H2O
• Excretion K
• Excretion Mg2

• Collagen
• deposition
• Fibrosis
• - myocardium
• - vessels

Edema
Arrhythmias
38
Spironolactone
Annual Mortality Aldactone 18 Placebo 23
Survival
Aldactone
N 1663 NYHA III-IV Mean follow-up 2 y
p lt 0.0001
RALES NEJM 1999341709
Placebo
months
39

• Spironolactone. Indications
• Recent or current symptoms despite ACE-i,
  diuretics, dig. and b-blockers
• AHA / ACC HF guidelines 2001
• Recommended in advanced heart failure (III-IV),
  in addition to ACE-i and diuretics
• Hypokalemia
• ESC HF guidelines 2001

40

• Spironolactone. Practical use
• Do not use if hyperkalemia, renal insuf.
• Monitor serum K at frequent intervals
• Start ACE-i first
• Start with 25 mg / 24h
• If K gt5.5 mmol/L, reduce to 25 mg / 48h
• If K is low or stable consider 50 mg / day
• New studies in progress

41

Angiotensin II Receptor Blockers (ARB)
RENIN
Angiotensin IANGIOTENSIN II

Angiotensinogen
ACE
Other pathways
AT1 Receptor Blockers
RECEPTORS
AT1
AT2
Vasoconstriction
Proliferative Action
Vasodilatation
Antiproliferative Action
42
Angiotensin II Receptor Blockers (ARB)

• Candesartan, Eprosartan, Irbesartan
• Losartan, Telmisartan, Valsartan
• Not indicated with beta blockers
• Indicated in patients intolerant to ACE-I

AHA / ACC HF guidelines 2001 ESC HF guidelines
2001
43

• Positive Inotropes
• Digitalis
• Sympathomimetics
• Catecholamines
• B-adrenergic agonists
• Phosphodiesterase inhibitors
• Amrinone, Milrinone, Enoximone
• Calcium sensitizers
• Levosimendan, Pimobendan

44
Positive Inotropic Therapy

• May increase mortality
• Exception Digoxin, Levosimendan
• Use only in refractory CHF
• NOT for use as chronic therapy

45
Digitalis. Mechanism of Action Blocks Na / K
ATPase gt Ca Inotropic effect Natriuresis
Neurohormonal control
NEJM 1988318358
46
Digitalis. Clinical Effects

• Improve symptoms
• Modest reduction in hospitalization
• Does not improve survival

47
Digitalis. Indications When no adequate
response to ACE-i diuretics beta-blockers
AHA / ACC Guidelines 2001 In combination with
ACE-i diuretics if persisting symptoms ESC
Guidelines 2001 AF, to slow AV conduction Dose
0.125 to 0.250 mg / day
48

Digitalis
Mortality
Placebo n3403
p 0.8
N6800 NYHA II-III
Digoxin n3397
0
48
12
24
36
DIG N Engl J Med 1997336525
Months
49

• Diuretics. Indications
• 1. Symptomatic HF, with fluid retention
• Edema
• Dyspnea
• Lung Rales
• Jugular distension
• Hepatomegaly
• Pulmonary edema (Xray)

AHA / ACC HF guidelines 2001 ESC HF guidelines
2001
50

• Loop Diuretics / Thiazides. Practical Use
• Start with variable dose. Titrate to achieve dry
  weight
• Monitor serum K at frequent intervals
• Reduce dose when fluid retention is controlled
• Teach the patient when, how to change dose
• Combine to overcome resistance
• Do not use alone

51
Sharpe N. Heart failure. Martin Dunitz
200043 Kubo SH , et al. Am J Cardiol
1987601322 MRFIT, JAMA 19822481465 Pool
Wilson. Heart failure. Churchill Livinston
1997635
52

• Diuretic Resistance
• Neurohormonal activation
• Rebound Na uptake after volume loss
• Hypertrophy of distal nephron
• Reduced tubular secretion (renal failure,
  NSAIDs)
• Decreased renal perfusion (low output)
• Altered absortion of diuretic
• Noncompliance with drugs

Brater NEJM 1998339387 Kramer et al. Am J Med
199910690
53
Managing Resistance to Diuretics Restrict
Na/H2O intake (Monitor Natremia) Increase dose
(individual dose, frequency, i.v.) Combine
furosemide thiazide / spiro / metolazone
Dopamine (increase cardiac output) Reduce dose
of ACE-i Ultrafiltration
Motwani et al Circulation 199286439
54
Drugs to Avoid (may increase symptoms, mortality)

• Inotropes, long term / intermittent
• Antiarrhythmics (except amiodarone)
• Calcium antagonists (except amlodipine)
• Non-steroidal antiinflammatory drugs (NSAIDS)
• Tricyclic antidepressants
• Corticosteroids
• Lithium

ESC HF guidelines 2001
55

• Refractory End-Stage HF
• Review etiology, treatment aggrav. factors
• Control fluid retention
• Resistance to diuretics
• Ultrafiltration ?
• iv inotropics / vasodilators during
  decompensation
• Consider resynchronization
• Consider mechanical assist devices
• Consider heart transplantation

56
Cardiac Resynchronization Therapy in Patients
With Severe Systolic Heart Failure

• For patients who have left ventricular ejection
  fraction (LVEF) less than or equal to 35, a QRS
  duration greater than or equal to 0.12 seconds,
  and sinus rhythm, cardiac resynchronization
  therapy (CRT) with or without an ICD is indicated
  for the treatment of New York Heart Association
  (NYHA) functional Class III or ambulatory Class
  IV heart failure symptoms on optimal recommended
  medical therapy

57
Indications for CRT Therapy
58

• Heart Transplant. Indications
• Refractory cardiogenic shock
• Documented dependence on IV inotropic support to
  maintain adequate organ perfusion
• Peak VO2 lt 10 ml / kg / min
• Severe symptoms of ischemia not amenable to
  revascularization
• Recurrent symptomatic ventricular arrhythmias
  refractory to all therapeutic modalities
• Contraindications age, severe comorbidity

59

• Ventricular Arrhythmias / Sudden Death
• Antiarrhythmics ineffective (may increase
  mortality)
• Amiodarone do not improve survival
• ?-blockers reduce all cause mortality and SD
• Control ischemia
• Control electrolyte disturbances
• ICD (Implantable Cardiac Defibrillator)
• In secondary prevention of SD
• In sustained, hemodynamic destabilizing VT
• Ongoing research will establish new indications

60
Device Therapy for Stage C HFrEF (cont.)
Recommendations COR LOE
ICD therapy is recommended for primary prevention of SCD in selected patients with HFrEF at least 40 days post-MI with LVEF 35, and NYHA class II or III symptoms on chronic GDMT, who are expected to live 1 year I A
CRT is indicated for patients who have LVEF 35, sinus rhythm, LBBB with a QRS 150 ms I A (NYHA class III/IV)
CRT is indicated for patients who have LVEF 35, sinus rhythm, LBBB with a QRS 150 ms I B (NYHA class II)
ICD therapy is recommended for primary prevention of SCD in selected patients with HFrEF at least 40 days post-MI with LVEF 30, and NYHA class I symptoms while receiving GDMT, who are expected to live 1 year I B
CRT can be useful for patients who have LVEF 35, sinus rhythm, a non-LBBB pattern with a QRS 150 ms, and NYHA class III/ambulatory class IV symptoms on GDMT. IIa A
CRT can be useful for patients who have LVEF 35, sinus rhythm, LBBB with a QRS 120 to 149 ms, and NYHA class II, III or ambulatory IV symptoms on GDMT IIa   B
CRT can be useful in patients with AF and LVEF 35 on GDMT if a) the patient requires ventricular pacing or otherwise meets CRT criteria and b) AV nodal ablation or rate control allows near 100 ventricular pacing with CRT IIa B
61

• Diastolic Heart Failure
• Incorrect diagnosis of HF
• Inaccurate measurement of LVEF
• Primary valvular disease
• Restrictive (infiltrative) cardiomyopathies
  (Amyloidosis)
• Pericardial constriction
• Episodic or reversible LV systolic dysfunction
• Severe hypertension, ischemia
• High output states Anemia, thyrotoxicosis, etc
• Chronic pulmonary disease with right HF
• Pulmonary hypertension
• Atrial myxoma
• LV Hypertrophy
• Diastolic dysfunction of uncertain origin

62
Treatment of HFpEF
Recommendations COR LOE
Systolic and diastolic blood pressure should be controlled according to published clinical practice guidelines I B
Diuretics should be used for relief of symptoms due to volume overload I C
Coronary revascularization for patients with CAD in whom angina or demonstrable myocardial ischemia is present despite GDMT IIa   C
Management of AF according to published clinical practice guidelines for HFpEF to improve symptomatic HF IIa C
Use of beta-blocking agents, ACE inhibitors, and ARBs for hypertension in HFpEF IIa C
ARBs might be considered to decrease hospitalizations in HFpEF IIb B
Nutritional supplementation is not recommended in HFpEF III No Benefit C
63
Stages, Phenotypes and Treatment of HF