4/9/2014

Learning goals
Definition Epidemiology Determinants of cardiac performance Types of HF Etiology of HF Pathophysiology Prognosis Diagnosis Management

Chronic Heart Failure

Mohammed AlAl-Kebsi Master Degree-2014

Definition

Epidemiology
The overall prevalence of heart failure was estimated as 1.0% to 1.6%, rising from 0.1% in the 30-39 age range to 4.2% at 70- 79.

Heart failure is a clinical syndrome characterized by inadequate systemic perfusion to meet the body's metabolic demands as a result of impaired cardiac pump function.

Hospital admissions Patients with HF account for about 1,000,000 hospital admissions annually. Hospital Re-admissions One-third of these patients are re-admitted within 90 days for recurrent decompensation. Mortality Although much progress has been made in the treatment of HF, there is a 20% overall annual mortality, particularly in patients with NYHA IV symptoms. Approximately 50% of patients with severe heart failure due to LV dysfunction will die within 2 years. Many patients die suddenly from malignant ventricular arrhythmias or MI.

4/9/2014

Determinants of cardiac performance

1. Preload
Is the stress on the myocardial wall in an intact ventricle at the end of diastole - just prior to ventricular contraction - this is related to the end diastolic pressure and volume - which ultimately affect the muscle fiber length.

Determinants of cardiac performance

3. Contractility
Is also referred to as the inotropic state. When preload and afterload are constant, increasing contractility (with drugs for example) can augment the cardiac output .

2. Afterload
Is the tension or "wall stress" acting after the onset of shortening/contraction - and is primarily mediated by arterial pressure. As arterial pressure/resistance rises, stroke volume falls - which can cause acute exacerbations of CHF in patients with failing hearts, especially those with diastolic dysfunction .

4. Others
Stroke volume (SV) - the amount of blood ejected with each systole Cardiac output (CO) - which is [SV] x [Heart Rate] (beats per min) = CO (normal is ~5-6 L/M) End diastolic volume (EDV). Ejection fraction (i.e., the portion of blood ejected with each systole) which is the [SV divided by EDV] x 100 (normal is 55-65%.

Types of HF Syndrome
1. Systolic Dysfunction (SHF) vs. Diastolic Dysfunction (DHF): Systolic failure is a disorder of impaired myocardial contractility - leading to a reduced ejection fraction and a reduced stroke volume. This is associated with an elevated end diastolic left ventricular volume and pressure. Diastolic failure is a disorder of impaired myocardial relaxation leading to reduced filling in diastole and an elevated diastolic pressure. The ejection fraction may be normal or reduced.

Types of HF Syndrome
2. Forward HF vs. Backward HF:
Backward failure is characterised by increased systemic venous pressure in the right heart side and increased pulmonary venous pressure in the left heart side. For example, development of fluid retention raises the workload and thereby worsens backward failure. Forward failure shows a reduced blood flow volume (ejection) into the aorta (left heart side) and pulmonary artery (right heart side). Forward heart failure worsens by increased vasoconstriction which further reduces the ejection. In contrast, vasodilators improve it.

4/9/2014

3. Left sided HF vs. Right sided HF: Left sided HF There is a reduction in the left ventricular output and/or an increase in the left atrial or pulmonary venous pressure. Right sided HF There is a reduction in RV output. Causes of isolated right heart failure include chronic lung disease (cor pulmonale), multiple pulmonary emboli and pulmonary valvular stenosis. Bivent.HF Failure of the left and right heart may develop because the disease process (e.g. dilated cardiomyopathy or ischaemic heart disease) affects both ventricles, or because disease of the left heart leads to chronic elevation of the left atrial pressure, pulmonary hypertension and right heart failure. 4. High-output failure A rare cause of heart failure caused by thyrotoxicosis, arteriovenous fistulae, Paget's disease, pregnancy, or severe chronic anemia. In such cases, additional causes of heart failure are often present.

5. Acute Vs chronic HF: Acute HF means acute onset or decompansation of CHF characterized by signs of pulmonary and /or peripheral congestion, including pulmonary edema and/or peripheral edema with /or without sign of peripheral hyoperfusion.

Etiology of HF
Coronary artery disease Myocardial infarction Ischaemia Hypertension Arrhythmias Tachycardia Bradycardia (complete heart block, the sick sinus syndrome) Loss of atrial transportfor example, atrial fibrillation
NYHA I

ACC/AHA Guidelines
Heart Failure Classification
NYHA II NYHA III NYHA IV

Cardiomyopathy Alcohol and drugs Dilated (congestive) Alcohol High output failure Hypertrophic/obstructive Cardiac depressant drugs fistulae, ( blockers, Anaemia, thyrotoxicosis, arteriovenous Restrictivefor example, amyloidosis, sarcoidosis,haemochromatosis antagonists) Pagets disease Obliterative Pericardial disease Valvular and congenital heart disease Constrictive pericarditis Mitral valve diseasePericardial effusion Aortic valve disease right heart failure Atrial septal defect, Primary ventricular septal defect Pulmonary hypertensionfor example, pulmonary embolism, cor pulmonale, Tricuspid incompetence

calcium

No limitation in physical activity Slight limitation in physical More marked limitation of Unable to carry out any despite presence of heart activity. More strenuous activity which interferes withphysical activity without disease. activity causes shortness of work.Walking on the flat symptoms. Patients This can be suspected only if breathexample, walking produces symptoms are breathless at rest . there is a history of heart disease on steep inclines and several which is confirmed by flights of steps. Patients in investigations example, this group can continue to echocardiography have analmost normal lifestyle and employment

ASYPTOMATIC

MILD

MODERATE

SEVERE

4/9/2014

ACC/AHA Guidelines
Heart Failure Classification
Stage A At high risk for HF but without structural heart disease or symptoms of HF Stage B Structural heart disease but without symptoms of HF Stage C Structural heart disease with prior or current symptoms of HF Stage D Refractory HF requiring specialized interventions

Pathophysiology of HF
In left ventricular systolic dysfunction, regardless of the etiology, cardiac output is low and pulmonary pressures are high, leading to pulmonary congestion. Initially, as a direct result of decrease cardiac output and systemic perfusion, the body activates several neurohormonal pathways in order to increase circulating blood volume. This response is adaptive and designed to preserve normal blood flow to systemic organs. over time, these responses can become maladaptive or counterproductive, leading to progression of the disease and worsening of symptoms.

e.g., Patients with: Hypertension Diabetes mellius or Patients Using cardiotoxins With FHx CM

Structural Heart Disease

e.g., Patients with: Previous MI Symptoms of HF LV systolic develop dysfunction Asymptomatic valvular disease

e.g., Patients with: Known structural heart disease Shortness of breath and fatigue, reduced exercise tolerance

Refractory symptoms of HF at rest

e.g., Patients who have symptoms at rest despite maximal medical therapy (e.g., those who are recurrently hospitalized or cannot be safely discharged from hospital without specialized interventions)

Pathophysiology of HF

Vasopressin
ReninRenin angiotensin system

sympathetic nervous system Adaptive Maladaptive mechanism mechanism

Cytokines

Aldosterone

Endothelin

4/9/2014

Pathophysiology of HF
The sympathetic nervous system Increases heart rate and contractility, both of which increase cardiac output. Circulating catecholamines also cause arteriolar vasoconstriction in non essential vascular beds and stimulate secretion of renin. Unfortunately, catecholamines aggravate ischemia, potentiate arrhythmias, promote cardiac remodeling, and are directly toxic to myocytes.

Pathophysiology of HF
ReninRenin -angiotensin system: system Stimulation of the reninrenin-angiotensin system as a result of increased sympathetic stimulation and decreased renal perfusion results in further arteriolar vasoconstriction, sodium and water retention, and release of aldosterone. aldosterone . Aldosterone: Aldosterone : Increased aldosterone, aldosterone, in turn, leads to sodium and water retention, endothelial dysfunction and organ fibrosis. fibrosis.

Pathophysiology of HF
Vasopressin In heart failure, baroreceptor and osmotic stimuli lead to Vasopressin: vasopressin release from the hypothalamus causing reabsorption of water in the renal collecting duct. Endothelin: endolthellin levels are elevated in heart failure and correlate Endothelin: with severity of disease and prognosis. Endothelin is an endogenous vasoconstrictor and growth factor. Cytokines: Levels of the propro-inflammatory cytokines also are elevated in heart failure, and contribute to cardiac cachexia and apoptosis.

Pathophysiology of HF
Although these neurohormonal pathways initially are compensatory and beneficial, eventually, they are deleterious, and neurohormonal modulation is the basis for modern treatment for heart failure. Enhanced neurohormonal stimulation of the myocardium also causes apoptosis or programmed cell death, worsening of ventricular contractility and death. With continuous neurohormonal stimulation, the left ventricle undergoes remodeling consisting of left ventricular dilatation and hypertrophy. Left ventricular chamber dilatation causes increased wall tension, worsens subendocardial myocardial perfusion, and may provoke ischemia in patients with coronary atherosclerosis. Furthermore, left ventricular chamber dilatation may cause separation of the mitral leaflets and mitral regurgitation leading to pulmonary congestion.

4/9/2014

Pathophysiology of HF

Pathophysiology of HF
In contrast, natriuretic peptides are hormones released by secretory granules in cardiac myocytes. They have a beneficial influence in heart failure, including systemic and pulmonary vasodilation, enhanced sodium and water excretion, and suppression of other neurohormones.

Pathophysiology of diastolic HF

Pathophysiology of HF

<100 pg/mL, then HF is highly unlikely (NPV = 90%). >500 pg/mL, then HF is highly likely (PPV = 90%) 100500 pg/mL, consider the baseline BNP is elevated due to stable underlying dysfunction, right ventricular failure from cor pulmonale, acute pulmonary embolism, or renal failure

In diastolic dysfunction, the primary abnormality is impaired left ventricular relaxation causing high diastolic pressures and poor filling of the ventricles. In order to increase diastolic filling, left atrial pressure increases until it exceeds the hydrostatic and oncotic pressures in the pulmonary capillaries and pulmonary edema ensues. As a result, patients are often symptomatic with exertion when increased heart rate reduces left ventricular filling time and circulating catecholamines worsen diastolic dysfunction.

4/9/2014

Precipitating causes of heart failure

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Arrhythmias, especially atrial fibrillation Infections (especially pneumonia) Acute myocardial infarction Angina pectoris or recurrent myocardial ischaemia Anaemia Alcohol excess Iatrogenic causefor example, postoperative fluid replacement or administration of steroids or non steroidal anti inflammatory drugs Poor drug compliance, especially in antihypertensive treatment Thyroid disordersfor example, thyrotoxicosis Pulmonary embolism Pregnancy Administration of a drug with negative inotropic properties (e.g. blocker) or fluid-retaining properties (e.g. non-steroidal antiinflammatory drugs, corticosteroids) Intravenous fluid overload, e.g. post-operative i.v. infusion

Complications of heart failure

1. ArrhythmiasAtrial fibrillation; ventricular arrhythmias (ventricular tachycardia, VF); bradyarrhythmias 2. ThromboembolismStroke; peripheral embolism; deep venous thrombosis; pulmonary embolism 3. GastrointestinalHepatic congestion and hepatic dysfunction; malabsorption 4. MusculoskeletalMuscle wasting 5. RespiratoryPulmonary congestion; respiratory muscle weakness; pulmonary hypertension (rare) 6. Renal failure due to : Low cardiac output- Diuretics (as side effect) 7. Hypokalemia due to : High aldestrone levels- Potasium losing diuretics 8. Hyperkalemia due to: Drugs such as Sprinolactone +ACEI- R. dysfunction 9. Sudden death in 50% of Pt.s because of V.F

13.

Prognosis of HF

Morbidity and mortality for all grades of symptomatic chronic heart failure are high, with a 20-30% one year mortality in mild to moderate heart failure and a greater than 50% one year mortality in severe heart failure.

Diagnosis Clinical Assessment

4/9/2014

The Essential or Basic Components of the Heart Failure Examination General appearance Vital signs (blood pressure and heart rate) in recumbent and upright positions Respiratory rate and pattern and body temperature as needed or observed Jugular venous pressure and hepatojugular reflux Auscultation of chest, percussion as needed Precordial palpation and auscultation Liver span (cephalocaudal dimension at midclavicular line) and tenderness Examination for peripheral edema and perfusion As needed or observed Skin appearance and temperature (to touch) of hands and feet Pulse character, contour, and duration (carotid and/or femoral sites)

Symptoms and signs in heart failure

Symptoms
Dyspnic, Orthopnic with Paroxysmal nocturnal dyspnoea. Reduced exercise tolerance, lethargy, fatigue Nocturnal cough Wheeze Ankle swelling Anorexia caused by combination of anorexia

Signs
Cachexia and muscle wasting Tachycardia Pulsus alternans Elevated jugular venous pressure Displaced apex beat Right ventricular heave Crepitations or wheeze Third heart sound Oedema Hepatomegaly (tender) Ascites

and impaired intestinal absorption due to intestinal congestion; poor tissue perfusion due to a low cardiac output ; and skeletal muscle atrophy due to immobility.

Symptoms of chronic heart failure Fermingham Criteria For Diagnosis of HF

Symptoms & signs of low cardiac output
Fatigue Poor effort tolerance Cold peripheries Oligouria Fainting or confusion

Major Criteria
Paroxysmal Nocturnal Dyspnea Neck veins distension Crepitation Acute pulmonary edema S3 gallop Increase venous retuern

Minor criteria
Pedal edema Night cough Dyspnea on exertion Hepatomegaly Pleural effusion Tachycardia Decrease vital capacity by 1/3 of normal

Symptoms & signs of pulmonary venous congestion

Dyspnea Orthopnea PND

Symptoms & signs of systemic venous congestion

Right Hypochondrial-epigastric pain, Dyspepsia, Nausea , Vomiting, Lower limbs edema , Scrotal edema. Ascites. pleural effusion.

Diagnosis achieved by: 1 major+2 minors

4/9/2014

Investigations if heart failure is suspected

Initial investigations
x x x x x Chest radiography Electrocardiography Echocardiography, including Doppler studies Haematology tests Serum biochemistry, including renal function and glucose concentrations, liver function tests, and thyroid function tests x Cardiac enzymes (if recent infarction is suspected), BNP.

Investigations

Other investigations
X Radionuclide imaging x Cardiopulmonary exercise testing x Cardiac catheterisation x Myocardial biopsyfor example, in suspected myocarditis

HEART FAILURE TREATMENT: GENERAL PRINCIPLES

Make or confirm appropriate diagnosis Stage syndrome severity Treat underlying diseases Prognostic benefits (mortality) vs symptomatic benefits. Stop drugs that have no proven benefit or that are potentially detrimental Begin therapeutic regimens with proven efficacy (titrate to appropriate doses) Prescribe rational polypharmacy Remember non pharmacologic approaches

Management of H.F.

4/9/2014

Prevention
Management:
Prevention Treatment with: Pharmacologic therapy Non-pharmacologic therapy Addressing all primary causes of cardiac disease eventually leading to HF
Hypertension Coronary heart disease Valvular heart disease Metabolic, toxic, or immunological heart disease

Treatment objectives

Management:
Prevention Treatment with: Pharmacologic therapy Non-pharmacologic therapy

Survival Morbidity Exercise capacity Quality of life Neurohormonal changes Progression of CHF Symptoms

10

4/9/2014

What we have?
In fact, there was 19 RCTs were published in the last 4 years.
Drug therapy trials. Few trial with devices. 2 important surgical trials. Couple of new trials on lifestyle, nonpharmacological measures. one looking at exercise, other at disease self management.

HF-REF: Drugs treatment 2012

Systolic heart failure (NYHA II-IV)

Treatment options Other treatment with less certain benefits

Preserved ejection fraction (HF-PEF)

European Heart Journal (2012) 33, 17871847 doi:10.1093/eurheartj/ehs104

11

4/9/2014

ACE Inhibitors in Heart Failure:

SOLVD Prevention (Asymptomatic LVD)
20% 29% death or HF hosp. death or new HF

CONSENSUS (Severe Heart Failure)

40% 31% mortality at 6 mos. mortality at 1 year

1. Angiotensin Converting Enzyme Inhibitors (ACE-inhibitors)

Block the renin-aldosterone-angiotensin system by inhibiting the conversion of angiotensin I to angiotensin II vasodilation and Na+ retention bradykinin degradation its level PG secretion & NO Decrease cardiac preload & afterload Major anti-remodeling effects on myocardium and vessels Mainstay in HF: they improve cardiac function, symptoms, and survival

SOLVD Treatment (Chronic Heart Failure)

16% mortality

27% mortality at end of study

No difference in incidence of sudden cardiac death

SOLVD Investigators. N Engl J Med 1992;327:685-91 SOLVD Investigators. N Engl J Med 1991;325:293-302 CONSENSUS Study Trial Group. N Engl J Med 1987;316:1429-35

Angiotensin Converting Enzyme Inhibitors (ACE-inhibitors)

Managing side effects

Cough (decreased catabolism of bradykinin) Hypotension ?? symptomatic, discontinue nitrates, calcium channel blockers, ? reduce diuretic dose Taste disturbance

12

4/9/2014

Precautions in ACEI
Low dose Avoid NSAIDs Follow closely for worsening renal dysfunction and/or hyperkalaemia Avoid in more severe renal impairment Consider combination Nitrate/Hydralazine as alternative
US

Effect of Beta Blockade on Outcome in Patients With HF and Post-MI LVD

Study Carvedilol1 Drug carvedilol bisoprolol metoprolol succinate carvedilol Carvedilol HF Severity mild/ moderate moderate/ severe mild/ moderate severe post-MI LVD Target Dose (mg) 6.2525 BID 10 QD 200 QD 25 BID 25 BID Outcome 48% disease progression (p= .007) 34% mortality (p <.0001) 34% mortality (p = .0062) 35% mortality (p = .0014) 23% mortality (p =.031)

CIBIS-II2 MERIT-HF3 COPERNICUS4 CAPRICORN5

1Colucci

WS et al. Circulation 1196;94:2800-6. 2CIBIS II Investigators. Lancet 1999;353:9-13. Study Group. Lancet 1999;353:2001-7. 4Packer M et al. N Engl J Med 2001;344 1651-8. 5The CAPRICORN Investigators. Lancet 2001;357:1385-90..
3MERIT-HF

Beta-blockers
Traditionally were contraindicated in HF. Now another mainstay in HF: Improve LV function and symptoms Improve survival The contraindications are severe decompensated HF; severe asthma, complete heart block, shock. Agents approved for HF: Carvedilol, Metoprolol succinate Bisoprolol, nebevilol.

Beta-blockers
It should be recognized that symptomatic improvement may not be evident for 23 months after initiating therapy with -blockers. However, -blocker therapy may reduce the risk of disease progression even if symptomatic improvement is not evident. Dosages are not adjusted according to response but instead are increased as tolerated to a prespecified target dose. Once titrated to the target or highest tolerated dosage, therapy generally can be maintained at this level long term.

13

4/9/2014

Initiation of -Blockers
Initiate Treatment when Patients are:
At their dry weight, without signs of fluid overload On stable doses of diuretics On an ACE-Inhibitor (at least low-dose)

Managing side effects

Worsening Heart Failure - up diuretics Worsening breathlessness (bronchospasm related) Symptomatic Hypotension- look at other meds before reducing B-Blocker. Excessive Bradycardia Fatigue; cold extremities; sleep disturbance Glucose tolerance in Diabetics

Low and Slow

Start low Increase the dose gradually (every 2-4 weeks)

NYHA Class:
NYHA class I to IV (once euvolaemic)

Advise Patients:
May feel worse before feeling better Daily weights If necessary, adjust diuretics to maintain pretreatment weight Not to stop drug suddenly

Use of best beta-blocker in various settings

Aldosterone antagonists

14

4/9/2014

What about patients with mild HF?

MRAs?

RALES EPHESUS

Post MI

Severity of heart failure

Primary endpoint cardiovascular death or hospitalization for HF 37%

Reductions were also seen in rates of death from any cause (24%), cardiovascular death (24%), hospitalization for any reason (23%), and HF hospitalization (42%).

15

4/9/2014

Aldosterone antagonists
Block aldosterone receptors Can be used in advanced HF, to further inhibit the R-A-A system after complete uptitration of ACE-inhibitors Check often for risk of hyperkalemia Available agents: spironolactone, eplerenone

Caution with Aldosterone Inhibitors

Spironolactone/Eplerenone are easy drugs to prescribe for HF!! Once a day and single dose (25mg/d) no titration Caution: Significant risk of hyperkalaemia (> 5%) Needs close monitoring 10% risk of gynaecomastia (vs <1% with eplerenone)

Aldosterone Antagonists
Current Recommendations in HF

Check K+ at one week, one month and every 3 months If K+ > 6.0 or Creatinine rising stop drug If painful gynaecomastia change to Eplerenone 25mg/d - Still has a risk of hyperkalaemia

16

4/9/2014

Angiotensin II antagonists
Comparable effect to ACE-inhibitors Fewer side effects than ACE-inhibitors Can be used in certain conditions when ACE-inhibitors are contraindicated (angioneurotic edema, cough) May be combined with ACE-inhibitors, provided BP is ok, to possibly improve survival and definitely reduce hospitalizations Commonly used agents: candesartan, losartan, valsartan

17

4/9/2014

Angiotensin II antagonists
1. 2. 3.

Other treatments recommended in selected patients with systolic EF

4. 5.

Are ARBs more effective than ACEACE-inhibitors? NO Are ARBs as effective as ACE inhibitors? PRO Is the combination of an ARB & an ACEACE-inhibitors more effective than ACEACEinhibitor monotherapy? YES Are ARBs effective in patients who cannot tolerate ACEACE-inhibitors? YES Are ARBs effective in patients with heart failure and preserved left ventricular function? NOT SURE??

Diuretics
The most effective symptomatic relief Usually shortshort-term IV therapy followed by longlong-term PO therapy Thiazides: Thiazides : HCTZ, chlorthalidone Loop diuretics: Furosemide, torasemide, , bumetanide, bumetanide, etacrynic acid Mixed agents: Metolazone, nesiritide

18

4/9/2014

Diuretics (practical points)

Effective at treating & controlling fluid retention, but do not prevent disease progression. If used alone can stimulate renin-angiotensin system & accelerate disease process. Goal to achieve dry weight using as low a dose of diuretic as possible. Titrate to weight & symptoms Flexible regime Self management / titration

Diuretics

Cautions with Diuretics

Hyponatraemia Hypokalaemia & low Mg Hypovolaemia & hypotension Drug Interaction reduce hypoglycaemic effect of oral hypoglycaemics > hyperglycaemia Gout Long-term resistance

Aspirin/oral anticoagulants
Aspirin is recommended in all patients with coronary heart disease, diabetes or any other established form of atherosclerotic disease, unless contraindicated by bleeding diathesis. Oral anticoagulants are recommended in patients with paroxysmal/permanent atrial fibrillation, or those with previous embolic events (eg in poor LV contractilty) and hugely dilated LV.

19

4/9/2014

Antiarrhythmics
Most common cause of sudden cardiac death in HF is ventricular tachyarrhythmia Antiarrhythmic drugs may suppress PVC but may induce VT or VF!!! Only amiodarone has a reasonably safe profile in HF, but no impact of amiodarone on prognosis. Remember the many toxic effects of amiodarone: lung, thyroid, eye, liver

Digitalis glycosides (digoxin, digitoxin)

Their role has declined in recent years (DIG Study) Digitals does not affect mortality in CHF patients but causes significant: Reduction in hospitalization Reduction in symptoms of HF Actions: Positive inotropic effect Arrhythmogenic effect Vagotonic effect

Digoxin in high risk HF patients subgroup: HF hospitalization or HF mortality

20

4/9/2014

Digitalis glycosides (digoxin, digitoxin)

Digoxin levels should be 1.0 2.0 ng/dL, but narrow & variable therapeutic window (check serum!) Toxicity - non cardiac manifestations: Anorexia, nausea, vomiting, headache, xanthopsia sotoma, disorientation Toxicity - cardiac manifestations: Sinus bradycardia and arrest, A/V block (usually 2nd degree), atrial tachycardia with A/V block, development of junctional rhythm in patients with AF, PVC, VT/ VF (bi-directional VT)

Should we Use Digoxin

Digoxin does not reduce mortality. Modest reduction in rate of hospitalisation (NYHA class II/III) Consider as adjunctive therapy in NYHA class II-IV patients with persistent sx Low therapeutic-to-toxic range Decrease dose with advanced age, renal dysfunction, and women 0.125mg/d is probably optimal dose

Other treatments recommended in selected patients with systolic EF

(Vaso) Dilators: nitrates & hydralazine

Reduction of afterload by arteriolar vasodilatation (hydralazin) LVEDP, O2 consumption, myocardial perfusion, stroke volume and CO Reduction of preload by venous dilation (nitrates) venous return load on both ventricles Usually maximum benefit achieved by using both agents, but currently approved (in US).

21

4/9/2014

Nitrates/Hydralazine
Consider as a therapeutic option in patients intolerant of ACEI Renal insufficiency Compliance difficult Side-effects Dosing regimens
ISDN dose 40-60mg TID Hydralazine dose 25-100mg TID or QID

Other treatments recommended in selected patients with systolic EF

Other treatments recommended in selected patients with systolic EF

Effect of Ivabradine on outcomes in HF

22

4/9/2014

Effect of Ivabradine on outcomes

Other treatments recommended in selected patients with systolic EF

What will guidelines task force decide

Should all patients on maximally tolerated dose of beta blocker be considered for Ivabradine?

Should be considered to reduce the risk of HF hospitalization in patients in sinus rhythm with an EF 35%, a HR remaining 70 b.p.m., and persisting symptoms (NYHA class IIIV) despite treatment with an evidencebased dose of beta-blocker (or maximum tolerated dose below that), ACE inhibitor (or ARB), and an MRA (or ARB)

23

4/9/2014

Inotropes
Improve myocardial contractility ( adrenergic agonists, dopaminergic agents, phosphodiesterase inhibitors, calcium-channel sensitizers): dopamine, dobutamine, milrinone, amrinone, levosimendan Most studies showed long-term mortality with inotropic agents. Yet beneficial at short-term use for peripheral hypoperfusion +/- pulmonary edema refractory to diuretics and vasodilators Only use them in acute conditions such as cardiogenic shock, as bridge to another lasting intervention (eg transplant).

Invasive Non-surgical treatment in HF

Implantable cardioverter debribillators (ICD) Cardiac resynchronization therapy (CRT)

Implantable cardioverter debribillators (ICD)

Surgical management of HF
Type of surgery Reason

Patients with EF35% and CHF benefit from ICD (primary prevention) Patients with history of sustained VT or SCD benefit from ICD (secondary prevention) Patients with history of non-sustained VT and EF between 3040% electrophysiological testing ICD (primary prevention)

Coronary revascularisation (PTCA, CABG) Valve replacement (or repair) Cardiac transplantation Ventricular assist devices

Angina, reversible ischaemia, Significant valve disease (AS, MR) End stage heart failure Short term ventricular supporteg awaiting for transplantation Stem cells- cardiac reconstruction

Novel surgical techniques

24

4/9/2014

Cardiac transplant
It has become more widely used since the advances in immunosuppressive treatment Survival rate 1 year 80% - 90% 5 years 70% 10 years 50% Long list- problem with donors.

Non-pharmacological measures
Compliance: give careful advice about disease, treatment, and self help strategies Diet: ensure adequate general nutrition and, in obese patients, weight reduction Salt: advise patients to avoid high salt content foods and not to add salt (particularly in severe cases of CHF) Fluid: Advice overloaded patients and those with severe CHF to restrict their fluid intake Alcohol: advise moderate alcohol consumption. Smoking: avoid smoking. Exercise: regular exercise should be encouraged Vaccination: patients should consider influenza and pneumococcal vaccinations

TAILORED Therapy
Tailored : 1. Smart, fitted,
and well cut (clothes); 2. Made or adapted for a particular purpose or person (Oxford, 2nd 2005) I

Management
II III IV

25

4/9/2014

Evidence-Based Treatment Across the Continuum of Systolic LVD and HF

Control Volume Diuretics ACEI or ARB Improve Clinical Outcomes Aldosterone -Blocker Antagonist or ARB CRT an ICD* HDZN/ISDN*
*In selected patients

Samples of therapies been tested in HF with PEF

Treat Residual Symptoms Digoxin

Treatment of patients with Preserved ejection fraction (HF-PEF)

No treatment has yet been shown, convincingly, to reduce morbidity and mortality in patients with HF-PEF. Diuretics are used to relieve breathlessness and oedema as in HF-REF. Adequate treatment of hypertension and myocardial ischaemia is also considered to be important, as is control of the ventricular rate in patients with AF. The drugs that should be avoided in HF-REF should also be avoided in HF-PEF, with the exception of CCBs.

26

4/9/2014

Spironolactone (25mg/d) improved diastolic function. Did not improve exercise capacity, NYHA class, or quality of life No significant differences in death or hospitalization rates. Was safe and not associated with severe adverse events Can be considered in patients with diastolic heart failure for improving cardiac function and blood pressure control

Serum Potassium*

Potassium Hyperkalemia ( 5.5 mmol/L) Hypokalemia (<3.5 mmol/L)

Spiro 322 (18.7%) 279 (16.2%)

Placebo 157 (9.1%) 394 (22.9%)

P (chisq) <0.001 <0.001

TOPCAT is a multi-center, international, randomized, double blind placebo-controlled trial of the aldosterone antagonist, spironolactone, in 3,445 adult subjects with heart failure and left ventricular ejection fraction of at least 45%, recruited internationally from over 200 clinical centers in the US, Canada, Russia, Republic of Georgia, Argentina, and Brazil. Enrollment started in August 2006 and recently ended on January 31, 2012.

No deaths related to hyperkalemia were reported. *Monitoring at each dose change and visit (algorithm in Desai Am Heart J 2011)

27

4/9/2014

Summary
Spironolactone (N = 1722) Placebo (N = 1723)

Future management of HF-pEF

HR (95% CI) 0.89 (0.77-1.04) P=0.138 0.83 (0.69-0.99) P=0.042 Multiple HF Hosp P<0.01 320 (18.6%) 5.9/100pt-yr 206 (12.0%) 3.8/100pt-yr 351 (20.4%) 6.6/100pt-yr 245 (14.2%) 4.6/100pt-yr

Primary Outcome Hospitalization for Heart Failure

Conclusions: TOPCAT population with HFpEF:

Rx with spironolactone did not alter the 1composite Reductions in heart failure were observed Use of spironolactone in these patients requires careful monitoring of K+ and creatinine

Exercise training improves symptoms. Aldosterone receptor blockade no symptomatic benefit. Mortality Angiotensin receptor neprilysin inhibitor looks promising. End point study. Late Na inhibitor acute effect long term studies. Autonomic nervous system modulation.

Lifestyle and non-pharmacological/ device/ surgical intervention

HF-ACTION
Trial design: Patients with symptomatic systolic CHF on optimal medical therapy were randomized to either exercise training or usual medical care. Clinical outcomes were compared at 3 years. Results

(p = 0.26) 20 15 m 10 5 0 Change in 6-minute walk distance

Exercise training (n = 1,159)

(p < 0.0001) 1.0 0.7

12

13

No difference in mortality/hospitalizations between the two arms (HR 0.93, 95% CI 0.84-1.02, p = 0.13). On adjustment for other prognostic factors, was in exercise training arm (p = 0.03) CV mortality & CV hospitalizations (p = 0.14), 6-minute walk distance similar, but peak VO2 higher in the exercise training arm Serious side effects similar between two arms

ml/min/kg

0.5

0.1 0 Change in Peak VO2

Usual care (n = 1,172)

Conclusions
Prescribed exercise training program in patients with systolic CHF safe and effective, when added on to optimal medical therapy Strengthens current recommendations for exercise in CHF patients
OConnor CM, et al. JAMA 2009;301:1439-50

28

4/9/2014

The goals of treatment

To relieve symptoms and signs. Prevent hospital admission. Improve survival. Preventing HF hospitalization. Reductions in mortality and hospital admission rates.

Everything is clear?

29