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
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. Proinflammatory cytokines
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. Cool, pale, cyanotic extremities
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 enlargement>

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 > 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
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. II
Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in symptoms of HF.
III
Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes 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.

20. Aggravating Factors Medications New heart disease Myocardial ischemia
Pregnancy
Arrhythmias (AF)
Infections
Thromboembolism
Hyper/hypothyroidism
Endocarditis
Obesity
Hypertension
Physical activity
Dietary excess
Treatment of Heart Failure.
Correction of aggravating factors
Often a lack of response to conventional therapy for heart failure is due to the presence of uncorrected aggravating or precipitating factors. It is important to always consider the possibility of such factors, particularly in cases of refractory failure. AF: atrial fibrillation.

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 ?
Treatment of Heart Failure.
Correction of aggravating factors
Often a lack of response to conventional therapy for heart failure is due to the presence of uncorrected aggravating or precipitating factors. It is important to always consider the possibility of such factors, particularly in cases of refractory failure. AF: atrial fibrillation.

22. ACE-i. Mechanism of Action
VASOCONSTRICTION
VASODILATATION
ALDOSTERONE
PROSTAGLANDINS
VASOPRESSIN
Kininogen
tPA
SYMPATHETIC
Kallikrein
Angiotensinogen
RENIN
BRADYKININ
Treatment of Heart Failure
Angiotensin Converting-Enzyme Inhibitors (ACEI) :Mechanisms of action
ACE-inhibitors competitively block the converting enzyme that transforms angiotensin I into angiotensin II. The reduction in angiotensin II levels explains its arteriovenous vasodilatory actions, as angiotensin II is a potent vasoconstrictor that augments sympathetic tone in the arteriovenous system. Additionally, angiotensin causes vasopressin release and produces sodium and water retention, both through a direct renal effect and through the liberation of aldosterone. Since converting enzyme has a similar structure to kinase II that degrades bradykinin, ACE-inhibitors increase kinin levels that are potent vasodilators (E2 and F2) and increase release of fibrinolytic substances such as tPA.
Angiotensin I
A.C.E.
Inhibitor
Kininase II
ANGIOTENSIN II
Inactive Fragments

23. ACE-I. Clinical Effects
Improve symptoms
Reduce remodelling / progression
Reduce hospitalization
Improve survival
Treatment of Heart Failure.
Angiotensin Converting-Enzyme Inhibitors (ACEI): Mechanisms of action
ACE-inhibitors cause arteriovenous vasodilatation. Venodilation is accompanied by reduction in PAD, PCWP, and LVEDP. Arterial vasodilatation decreases SVR and MAP and increases cardiac output, ejection fraction, and exercise tolerance. Heart rate and contractility do not change, and, thus, double product and myocardial oxygen demand are decreased. These effects are more noticeable in patients with low sodium levels, in whom there is an increased plasma renin activity. Vasodilatation is seen in various vascular territories: renal, coronary, cerebral, and musculoskeletal (increasing exercise capacity). Additionally, ACE-inhibitors cause diuretic and natriuretic effects that are a consequence of the inhibition of angiotensin II and aldosterone synthesis, as well as the increase in cardiac output and renal perfusion.
It is now known that the magnitude and duration of blood pressure reduction correlates better with the activity of ACE in certain tissues (heart, vessels, kidney, adrenal, etc.) than with its plasma levels, which indicates that ACE-inhibitors act by inhibiting local tissue production of angiotensin II. Plasma levels of ACE are not good predictors of the magnitude of hemodynamic effects of ACE-inhibition.

24. Mortality Reduction with ACE-i
Study ACE-i Clinical Seting
CONSENSUS Enalapril CHF
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 Placebo Probabiility of Death Enalapril CONSENSUS Months 0.8 0.7
0.6
Probabiility of
Death
p< 0.001
0.5
0.4
p< 0.002
0.3
Enalapril
Treatment of Heart Failure.
Angiotensin Converting-Enzyme Inhibitors (ACEI): Survival
CONSENSUS. Prolonged administration of ACE-inhibitors reduces mortality in symptomatic heart failure. The first study to demonstrate this effect was CONSENSUS I. This graph shows the cumulative mortality curves of the treatment and placebo group in this randomized, double-blind trial. The study analyzed the effect of enalapril on prognosis of 253 patients with class IV heart failure, who also received digitalis, diuretics, and conventional vasodilators. At the end of 6 months of treatment, there was a clear-cut improvement in functional class, a reduction in the need for medications, and a 40% reduction in mortality (p<0.002). After 12 months the mortality reduction was 31% (p<0.001). Nonetheless, there were no differences in the incidence of sudden death between the two groups, or in the sub-group that received other conventional vasodilators. Another characteristic of this study was variability of the dose that was used for each patient (adjusted for tolerance and symptoms): mg/day. This aspect shows the importance of individualized treatment for heart failure patients.
The CONSENSUS Trial Study Group. N Engl J Med 1987;316:1429.
0.2
0.1 1 2 3 4 5 6 7 8 9 10 11 12
CONSENSUS
N Engl J Med 1987;316:1429
Months

26. ACE-i Mortality, % Years SAVE 30 Placebo 20 Captopril 10 1 2 3 4
Asymptomatic
ventricular
dysfunction post MI
Placebo
n=1116 20
Mortality, %
Captopril
n=1115
Treatment of Heart Failure
Angiotensin Converting-Enzyme Inhibitors (ACEI): Survival
SAVE (Survival and Ventricular Enlargement). Mortality curves in the SAVE study in patients with varying degrees of post-infarct ventricular dysfunction. In this study, 2231 patients with EF < 40% were randomized to receive captopril or placebo between 3 to 16 days after experiencing a transmural infarct. After 42 months, the captopril group had a significant reduction in overall mortality (-19%), number of reinfarctions (-25%), hospitalizations (-22%), and in the number of patients who developed clinical congestive heart failure. The mortality reduction appeared after 1 year of treatment.
Pfeffer MA et al. Survival and Ventricular Enlargement (SAVE) Study. NEngl J Med 1992;327:669. 10
n = 2231
days post AMI
EF < 40
mg / day
² -19%
p=0.019
SAVE
N Engl J Med 1992;327:669 1 2 3 4
Years

27. ACE-i. Indications Symptomatic heart failure
Asymptomatic ventricular dysfunction
- LVEF < %
Selected high risk subgroups
Treatment of Heart Failure
Angiotensin Converting-Enzyme Inhibits (ACEI)
Indications.
ACE-inhibitors probably constitute the cornerstone of drug therapy for heart failure, in that administration over time leads to amelioration of symptoms, beneficial hemodynamic changes, increased functional capacity, regression of structural changes, and, unequivocally, prolongation of survival. Thus, ACE-inhibitors are first-line therapy, not only in symptomatic heart failure patients, but also in patients with asymptomatic left ventricular dysfunction. The exact degree of ventricular dysfunction below which it is advisable to begin therapy with an ACE-inhibitor has not been defined; however, in general terms they can be helpful in patients with ejection fractions less than 35%.
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 to 2.5 / day 10 / day
AHA / ACC HF guidelines 2001

30. Hypotension (1st dose effect) Worsening renal function Hyperkalemia
ACE-I. Adverse Effects
Hypotension (1st dose effect)
Worsening renal function
Hyperkalemia
Cough
Angioedema
Rash, ageusia, neutropenia, …
Treatment of Heart Failure.
Angiotensin Converting-Enzyme Inhibitors (ACEI) : Undesirable Effects
These can be classified into two groups. One group includes those effects that are inherent to its mechanism of action, and therefore are common to all ACE-inhibitors. The other includes those effects that are related to the specific chemical structure of the drug. In this case, substitution of one ACE-inhibitor for another could possibly reduce the intensity of the adverse reaction (e.g. choosing an ACE-inhibitor without a sulfhydryl moiety).

31. ACE-I. Contraindications
Intolerance (angioedema, anuric renal fail.)
Bilateral renal artery stenosis
Pregnancy
Renal insufficiency (creatinine > 3 mg/dl)
Hyperkalemia (> 5,5 mmol/l)
Severe hypotension
Treatment of Heart Failure
Angiotensin Converting-Enzyme Inhibitors (ACEI)
Contraindications.
There are few absolute contraindications for the use of ACE-inhibitors. The most important one is the presence of renal artery stenosis. The most frequent contraindication is intolerance of the drug. Hypotension, the presence of renal insufficiency, or hyperkalemia limits their use, or the ability to administer adequate doses, in up to 20% of patients.

32. ß-Adrenergic Blockers Mechanism of action
Density of ß1 receptors
Inhibit cardiotoxicity of catecholamines
Neurohormonal activation HR
Antiischemic
Antihypertensive
Antiarrhythmic
Antioxidant, Antiproliferative
Treatment of congestive heart failure.
Possible benefits of beta adrenergic blockers
The use of ß-blockers in patients with heart failure is controversial. Nevertheless, this slide lists some of the potentially beneficial effects of these drugs for patients in heart failure.

33. ß-Adrenergic Blockers
100 90 80
Survival %
Carvedilol 70 p=
35% RR 60
Placebo
N = 2289
III-IV NYHA 50 4 8 12 16 20 24 28
COPERNICUS
NEJM 2001;344:1651
Months

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 / 24h 10 / 24h
Carvedilol / 12h 25 / 12h
Metoprolol succinnate 12,5-25 / 24h 200 / 24h
Start Low, Increase Slowly
Increase the dose every weeks 25

36. ß-Adrenergic Blockers Adverse Effects
Hypotension
Fluid retention / worsening heart failure
Fatigue
Bradycardia / heart block

37. - Spironolactone Aldosterone Inhibitors ALDOSTERONE Edema Fibrosis
Competitive antagonist of the
aldosterone receptor
(myocardium, arterial walls, kidney)
Retention Na+
Retention H2O
Excretion K+
Excretion Mg2+
Collagen
deposition
Fibrosis
- myocardium
- vessels
Edema
Treatment of congestive heart failure.
Aldosterone inhibitors: Mechanism of action
Aldosterone acts directly on specific receptors. At the renal level it produces retention of sodium and water, resulting in an increase in preload and afterload, edema formation and the appearance of symptoms of pulmonary and systemic venous congestion. In addition, it increases the elimination of potassium and magnesium, creating an electrolyte imbalance which may be responsible in part for cardiac arrhythmias. At the tissue level, aldosterone stimulates the production of collagen, being in large part responsible for the fibrosis that is found in hypertrophied myocardium and in the arterial walls of patients with heart failure. The beneficial effects of spironolactone derive from the direct and competitive blockade of specific aldosterone receptors. Aldosterone inhibitors therefore have three types of effects:
- Diuretic effect, which is most noticeable when fluid retention and increased levels of aldosterone are present.
- Antiarrhythmic effect, mediated by the correction of hypokalemia and hypomagnesemia.
- Antifibrotic effect. This effect, demonstrated in animal models, can contribute to a decrease in the progression of structural changes in patients with heart failure.
Arrhythmias

38. Spironolactone Survival RALES Aldactone N = 1663 NYHA III-IV
1.0
0.9
0.8
0.7
0.6
0.5
Annual Mortality
Aldactone 18%; Placebo 23%
Survival
Aldactone
N = 1663
NYHA III-IV
Mean follow-up 2 y
Mortality curves in the RALES study. (probably already shown by previous speaker). I will coment on the progressive increase in benefit and will made a comparation with the CIBIS-II results.
p <
RALES
NEJM 1999;341:709
months
Placebo 6 12 18 24 30 36

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+ >5.5 mmol/L, reduce to 25 mg / 48h
If K+ is low or stable consider 50 mg / day
New studies in progress

41. Angiotensin I ANGIOTENSIN II
Angiotensin II Receptor Blockers (ARB)
RENIN
Angiotensinogen
Angiotensin I ANGIOTENSIN II
ACE
Other pathways
AT1
Receptor
Blockers
Treatment of congestive heart failure.
Angiotensin II inhibitors
Angiotensin II has different effects mediated via specific receptors. There are two types of tissue receptors for angiotensin: AT1 and AT2. Stimulation of AT1 receptors has a proliferative and vasoconstrictor effect, while stimulation of AT2 receptors has the opposite effects, that is, vasodilatory and antiproliferative. In the treatment of heart failure, specific blockade of the AT1 receptors is desirable. Drugs which create a selective and competitive block of the AT1 receptors include:losartan, valsartan, irbersartan and candersartan.
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
Treatment of congestive heart failure.
Angiotensin II inhibitors
Drugs which create a selective and competitive block of the AT1 receptors include: losartan, valsartan, irbersartan and candersartan.
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
Treatment of heart failure.
Positive inotropic agents
The use of inotropic agents in heart failure is intended to increase contractility and cardiac output to meet the metabolic needs of the body. Theoretically, their use should be greatest in heart failure associated with a decrease in systolic function and marked cardiomegaly, depression of ejection fraction and elevated left ventricular filling pressure. In addition to the cardiac glycosides, other positive inotropic agents include: a) the sympathomimetics, represented by the ß1 agonists (which stimulate cardiac contractility) and ß2-adrenergics (vasodilators). Both groups increase the intracellular concentration of cAMP by stimulating the activity of adenylate cyclase which converts ATP to cAMP; b) Phosphodiesterase inhibitors, which inhibit the enzyme that breaks down cAMP, increase cardiac contractility and have arteriovenous vasodilatory effect; c) other ionotropic drugs including glucagon and Na+ channels agonists.

44. Positive Inotropic Therapy
May increase mortality
Exception: Digoxin, Levosimendan
Use only in refractory CHF
NOT for use as chronic therapy
Treatment of heart failure.
Inotropes: General problems
Positive inotropic drugs which increase cellular levels of cAMP have important proarrhythmic effects and seem to accelerate the progression of heart failure. Their hemodynamic effects decreased with prolonged treatment which suggests that they should not be used for chronic treatment. Safety and efficacy increases when they are used in low doses, with which the increase in contractility is slight. This points out that their beneficial effects probably do not depend on their positive inotropic action. The reduction in neurohumoral activation produced by digoxin and ibopamine, the antiarrhythmic action of Vesnarinone or the vasodilatory effects of dopamine, dobutamine or PDE III inhibitors may be more important than the increase in contractility that until recently was though to be their utility in the treatment of heart failure. With the exception of digoxin, chronic administration of these drugs increases mortality, so their use, in low doses, should be restricted to patients with refractory heart failure, with persistent symptoms despite treatment with combinations of other drugs. As it is precisely the sickest patients who manifest the increase in mortality, treatment with inotropic drugs is not likely to prolong the survival of these patients.

45. Digitalis. Mechanism of Action
Blocks Na+ / K+ ATPase => Ca+ +
• Inotropic effect
• Natriuresis
• Neurohormonal control
- Plasma Noradrenaline
- Peripheral nervous system activity
- RAAS activity
- Vagal tone
- Normalizes arterial baroreceptors
NEJM 1988;318:358

46. Digitalis. Clinical Effects
Improve symptoms
Modest reduction in hospitalization
Does not improve survival
Treatment of Heart Failure.
Angiotensin Converting-Enzyme Inhibitors (ACEI): Mechanisms of action
ACE-inhibitors cause arteriovenous vasodilatation. Venodilation is accompanied by reduction in PAD, PCWP, and LVEDP. Arterial vasodilatation decreases SVR and MAP and increases cardiac output, ejection fraction, and exercise tolerance. Heart rate and contractility do not change, and, thus, double product and myocardial oxygen demand are decreased. These effects are more noticeable in patients with low sodium levels, in whom there is an increased plasma renin activity. Vasodilatation is seen in various vascular territories: renal, coronary, cerebral, and musculoskeletal (increasing exercise capacity). Additionally, ACE-inhibitors cause diuretic and natriuretic effects that are a consequence of the inhibition of angiotensin II and aldosterone synthesis, as well as the increase in cardiac output and renal perfusion.
It is now known that the magnitude and duration of blood pressure reduction correlates better with the activity of ACE in certain tissues (heart, vessels, kidney, adrenal, etc.) than with its plasma levels, which indicates that ACE-inhibitors act by inhibiting local tissue production of angiotensin II. Plasma levels of ACE are not good predictors of the magnitude of hemodynamic effects of ACE-inhibition.

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 to mg / day

48. Digitalis Mortality % 50 40 30 20 10 Placebo Digoxin DIG 12 24 36 48
Mortality %
Placebo
n=3403
p = 0.8
N=6800
NYHA II-III
Treatment of heart failure.
Digoxin: Effect on survival
The results obtained from 3 controlled studies which included patients at low risk (The German and Austrian Xamoterol Study Group, 1988; The Captopril-Digoxin Multicenter Research Group, 1988; DiBianco et al., 1989) indicate that the mortality was similar in the group of patients with placebo. The results of the Digitalis Investigator Group-DIG study, which included 7788 patients with heart failure in sinus rhythm, functional class II-III and LVEF < 45%. The patients were treated with digoxin or placebo, in addition to conventional therapy over a mean of 37 months ( months). No differences in mortality were observed between the two treatment groups.
Am Coll Cardiol 1996
Digoxin
n=3397
DIG
N Engl J Med 1997;336:525 12 24 36 48
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 11

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. Thiazides, Loop Diuretics. Adverse Effects
• K+, Mg+ ( %) (sudden death ???)
• Na+
• Stimulation of neurohormonal activity
• Hyperuricemia ( %)
• Hypotension. Ototoxicity. Gastrointestinal. Alkalosis. Metabolic
Sharpe N. Heart failure. Martin Dunitz 2000;43
Kubo SH , et al. Am J Cardiol 1987;60:1322
MRFIT, JAMA 1982;248:1465
Pool Wilson. Heart failure. Churchill Livinston 1997;635

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 1998;339:387
Kramer et al. Am J Med 1999;106:90

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 1992;86:439

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
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
slide 37 57

58. Heart Transplant. Indications
Refractory cardiogenic shock
Documented dependence on IV inotropic support to maintain adequate organ perfusion
Peak VO2 < 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
Treatment of Heart Failure.
Correction of aggravating factors
Often a lack of response to conventional therapy for heart failure is due to the presence of uncorrected aggravating or precipitating factors. It is important to always consider the possibility of such factors, particularly in cases of refractory failure. AF: atrial fibrillation.

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
A (NYHA class III/IV)
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* 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
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
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
slide 37 60

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 C
Coronary revascularization for patients with CAD in whom angina or demonstrable myocardial ischemia is present despite GDMT
IIa
Management of AF according to published clinical practice guidelines for HFpEF to improve symptomatic HF
Use of beta-blocking agents, ACE inhibitors, and ARBs for hypertension in HFpEF
ARBs might be considered to decrease hospitalizations in HFpEF
IIb
Nutritional supplementation is not recommended in HFpEF
III: No Benefit

63. Stages, Phenotypes and Treatment of HF