Heart Failure: Difference between revisions

[[File:Foxglove_(digitalis).png|thumb|150px|right|Foxglove (digitalis), used as a medicine for heart failure]]

In 1628, William Harvey first described the circulation. Little understanding of the nature of heart failure (HF) could have existed before that time. There are accounts of a disease that now would be called heart failure, and herbal medicines like the ancient boiled bulb of squill, later on the broom plant (Cytisus scoparius) and the foxglove (Digitalis purpura) were used as diuretics to treat heart failure or dropsy (edema). The latter, foxglove, was described as a diuretic by William Withering in 1785 <cite>1</cite>. The essential glycoside substance digitalis of the leaves of the plant improves contractility of the cardiac muscle and has important parasympathetic effects, particularly on the atrioventricular node. In the 1950’s, thiazide diuretics were introduced, in the 1960’s furosemide. For a long time, diuretics and digitalis were the main treatment options for HF. After vasodilator therapy for HF was being introduced around 1960, the first randomized trial showing mortality benefit with nitrates and alphablockers for HF was published in 1986.  In 1975, the first ACE inhibitor captopril was developed and approved for human use in 1981, with a first randomized trial published in 1987. Spironolacton, introduced in 1959, was used (in low dose) for HF only after the introduction of ACE inhibitors.  Betablockers were scarcely used in heart failure when they started to be shown beneficial in the 70’s, but it was only in 1994 that the first randomized trial showed mortality benefit with betablockers.   

===Framingham heart study===  

In 1948, the Framingham heart study was launched. At its start, 5209 residents of the town Framingham in the US aged between 30 and 62 were included for assessing risk factors for cardiac disease at follow up in the study which is still continued today. This study is considered the most important longitudinal source of data on the epidemiology of heart failure.<cite>2</cite>

{| class="wikitable" borde="0" cellpadding="0" cellspacing="0" width="600px"

!colspan="2"|Table 1 Definition of heart failure

|colspan="2"|'''''Heart failure is a clinical syndrome in which patients have the following features:'''''

**Pleuraeffusion

**Peripheral oedema, **Hepatojugular reflux

The prevalence of HF in the Western world is estimated as 1 to 2%, and the incidence is around 5 to 10 per 1000 persons per year (7,9). Because at young age coronary heart disease is more prevalent in men, prevalence of HF is also higher in this group compared to age matched women. At older age, prevalence of HF is equal between sexes.  

Heart failure may become a chronic condition, in which HF is persistent, either with recurrences or with slow progression. A patient may be described as decompensated when chronic stable HF deteriorates.  Acute HF has traditionally been used to describe the nature of the clinical presentation, as severe or of recent onset. Different clinical presentations fall under this definition.  

Heart failure patients may be broadly classified into one of two groups, or a combination of both, depending on the left ventricular ejection fraction (LVEF). The LVEF is most often assessed with echocardiography (see table 3).  When the LVEF is less than 45%, systolic pump function is abnormal and it is named systolic HF <cite>3</cite>. If LVEF is preserved (>50%), symptoms are attributed to impaired relaxation of the heart during diastole and therefore is labeled as diastolic HF or HF with a preserved LVEF <cite>3</cite><cite>4</cite>. As a result of impaired relaxation, end diastolic pressure and subsequently left atrial- and pulmonary pressure will rise with subsequent alveolar pulmonary edema as a consequence. LF diastolic dysfunction may be present in asymptomatic patients, and it is considered an important precursor of heart failure <cite>5</cite>. Frequently, patients have both systolic and diastolic heart failure at the same time, but the term for this ailment is still systolic heart failure.  

HF is caused by a loss of cardiac pump function which can be due to a structural abnormality of the heart muscle (e.g. myocardial infarction) or a change in the heart function (and often structure) in response to an abnormal load (e.g. aortic valve stenosis). The relationship between loading the ventricle (by filling it) and its output was described by Frank and Starling in 1918 and has become the cornerstone in understanding heart failure and how to treat it. The relationship determines that by loading the heart (increasing its filling or its pressure) the output increases (Figure 1). A heart that has a lower output can be improved by increasing its volume and its loading pressure. This is what naturally happens (LV dilatation and increased filling pressure) when the heart doesn’t pump out enough volume, and in the first phase of disease compensates for the loss of contractility. It takes more energy from the heart to work at increased loading, but the heart has a reasonable energy reserve. In a chronic situation, remodeling of the heart progresses (by hypertrophy of myocytes and dilatation by increasing myocyte length and matrix changes), which in the long term leads to a further loss in function. The result is further increased loading pressures in the heart and by communicating the diastolic loading pressures to the left atrium and pulmonary veins, the pulmonary capillaries may become overloaded, to leak water to the lungs. That is the actual restriction towards further filling the heart as a tool to improve its function; even poor left ventricles may be filled more to increase their output <cite>6</cite> but the patients’ pulmonary capillaries cannot tolerate these hydrostatic pressures and start to leak water.  

[[Image:frank_starling.svg|thumb|right|400px|Figure 1 Frank-Starling curve]]

Hemodynamic explanations (the heart as a pump) use the concept of preload (filling) and afterload (workload of the heart, which is wall tension and arterial pressure or vascular resistance).  In this way, the progression of left sided heart failure towards right sided heart failure is explained as follows: prolonged left ventricular failure increases pressures in the left atrium (preload), which in time leads to a subsequent increased resistance in the pulmonary vascular system (which is the afterload of the right ventricle) and eventually may also lead to right ventricular failure.  

Another relevant issue is afterload of the left ventricle influencing the output of the heart: as the afterload of the aortic pressure also influences the timing of closure of the aortic valve, a high aortic pressure will close the aortic valve early and will therefore diminish the output. Decreasing (theoretically diastolic, but more practically systolic) aortic pressure will increase the stroke volume by later closure of the aortic valves. (Figure 2)

[[Image:pressure_volume_curve.svg|thumb|400px|''Figure 2 Effects of decreased afterload. Red arrows indicate aortic valve opening, which occurs later and at higher LV systolic pressure when the diastolic aortic pressure is higher. Blue arrows indicate closing of the aortic valve. Bidirectional arrows represent stroke volume. When aortic pressure is decreased, stroke volume increases as a result of a lower aortic pressure during closure of the aortic valve.]]

A decreased cardiac output leads to diminished renal perfusion and release of hormones in the RAA-system: renin released in the circulation by the renal juxtoglomerular apparatus, which is stimulating the cleavage of angiotensinogen into angiotensins I and II during passage through the lungs. Angiotensin II stimulates vasoconstriction in the kidneys, and in other vascular systems, increasing blood pressure; the second effect of angiotensins is stimulating the release of aldosterone from the adrenals into the plasma, which retains sodium from the kidney tubules in the blood and thereby water. The RAA –system, which works as a compensatory mechanism for heart failure to increase blood pressure and blood volume, also stimulates hypertrophy of muscle cells and stimulates the formation of fibrosis, which in the long term are detrimental to heart failure.  

 

The other compensatory mechanism for heart failure, stimulation of the sympathetic nervous system, increases heart rate to increase cardiac output, which is a powerful compensatory mechanism. However, chronic stimulation of the sympathetic nerves to the heart, leading to higher heart rates, is toxic to the heart, by continuous release of norepinephrin to the myocyte. In addition, by their continued stimulation, the betareceptors for norepinephrin are downregulated in heart failure, which further diminishes the function and functional reserve of the heart.

 

When a patient presents with symptoms of heart failure, it is worthwhile to have a dedicated diagnostic and therapeutic plan, in the order as indicated below (Figure 3). Clinical aspects are important for diagnosis, but the final diagnosis is only made after objective evidence of heart dysfunction.

Diagnosis of HF requires the simultaneous presence of at least 2 major criteria or 1 major criterion in conjunction with 2 minor criteria. The Framingham Heart Study criteria are 100% sensitive and 78% specific for identifying persons with definite congestive heart failure in an outpatient population <cite>10</cite>.

In general, correlation between the severity of symptoms and the severity of HF in terms of loss of maximal oxygen consumption is weak <cite>3</cite>. The New York Heart Association functional classification is used most frequently to classify the severity of HF (Table 2). Assessing severity is needed for the proper therapy/ medication to be chosen.  

===Additional diagnostic test===

In order to assist in diagnosing HF and differentiate between causes, the following modalities are available.  

In every patient suspected of HF, an electrocardiogram (ECG) should be performed. Several common abnormalities (including possible causes) indicative of HF on the ECG include but are not limited to: sinus tachy- or bradycardia, atrial tachycardia, -flutter, or –fibrillation, ventricular arrhythmias, ischemia (including myocardial infarction), abnormal Q waves, left ventricular hypertrophy, micro voltages, and QRS length >120 ms. Although an abnormal ECG (excluding arrhythmias) has a low positive predictive value for HF, a normal ECG is highly indicative of the absence of HF.

A chest X-ray is a part of the standard examination in potential HF patients. Importantly, the x-ray is a tool to detect cardiomegaly (defined as a cardiac: thoracic ratio of > 0,5) or other clues (redistribution, Kerley B-lines and pleural effusion) that indicate HF. Also, it is important to rule out other causes of dyspnoea.  

Echocardiography is the cornerstone in diagnosing HF, and should routinely be performed, because ventricular function can be evaluated accurately with this technique. It can provide objective evidence of a structural or functional abnormality of the heart at rest besides signs and symptoms typical of heart failure. Important parameters that can be assessed include, but are not limited to, wall motion, valve function, and left ventricular ejection fraction and diastolic function. Diastolic dysfunction might be an important finding in symptomatic patients with a preserved ejection fraction. Refer to Table 3 for common echocardiographic findings in HF. Transoesophageal echocardiography is indicated in patients with an inadequate thansthoracic echo window, suspected endocarditis, complicated valvular disease or to exclude a LV thrombus. If echocardiography provides inadequate information or in patients with suspected coronary artery disease, additional imaging includes CT scanning, cardiac magnetic resonance imaging or radionuclide imaging.

A standard blood assessment covers a complete blood count, electrolytes, renal function, glucose and liver function. Furthermore, a urinalysis and other tests depending on the clinical condition complete the laboratory assessment.  For example, cardiac troponins must be sampled if an ACS is in the differential diagnosis. In patients suspected of HF, values of natriuretic peptides (such as B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP)) can provide important information regarding diagnosis, management and prognosis of HF. Natriuretic peptides are enzymes, secreted by the atria or ventricles in response to myocardial wall stress. The most commonly used tests are the BNP and NT-proBNP measurements, which despite their different half-lifes in plasma, do not really differ in diagnostic ability. Cut-off values are different in acute settings with acute dyspnea than in chronic settings. Normal values are almost 100% specific, and exclude heart failure in patients > 18 year old. Abnormal values do not have a 100% predictive value, and objective evidence for heart failure is still needed. The values of BNP and NTproBNP are also used for evaluating prognosis in patients with known HF, in which higher values carry a worse prognosis.  

===Exercise test===  

An exercise test is not diagnostic for heart failure, but may be used to objectify ischemia as the cause of heart failure, or can be used to assess severity of heart failure, usually in conjunction with maximal oxygen uptake (VO_2max) measurement. This test is performed on a treadmill or on an bicycle ergo meter. The patient is asked to give maximal effort while the work load gradually increases. During the test, ECG is monitored for ischemia. When possible, oxygen consumption should be measured during the test. Not only is an oxygen consumption test a good tool to discriminate between lung- peripheral- or heart problems, the obtained maximal oxygen uptake (VO_2max) also has an important prognostic value.  

Heart catheterization is not always part of the routine diagnosis and work-up of patients with HF.  It should be considered however to exclude coronary heart disease (Class of recommendation IIa, level of evidence C, see table 4). Coronary angiography is recommended in patients at high risk of coronary artery disease  (Class of recommendation I, level of evidence C) and in HF patients with significant valvular disease (Class of recommendation IIa, level of evidence C).

 

===Coronary heart disease===

The most important cause (50% of the cases) of HF in the Western world is ischemic heart disease including myocardial infarction. These patients mainly suffer from systolic HF due to wall motion abnormalities of the affected and due to remodeling of the non-affected parts of the myocardium.  

In patients with a high systolic blood pressure (BP), the left ventricle faces an increased afterload (a higher workload pumping the blood against the increased vascular resistance). Over a certain period of time, this will lead to hypertrophy of the cardiac myocardium, and longer term remodeling may lead to pump function disorders (diastolic or systolic). In as many as 60-70% of patients suffering HF, hypertension is the primary or secondary cause.   

Atrial fibrillation is a common rhythm disorder in the elderly. With this condition, the atria do not contract in the coordinated fashion as they would in normal sinus rhythm, and therefore the atria never optimally empty. Normally, the ‘atrial kick’ contributes to around 15% of the stroke volume. The absence of the atrial kick during atrial fibrillation can contribute to a reduced LVEF. However, atrial fibrillation is seldomly the cause of heart failure, but more often a trigger of heart failure in already existing structural heart disease.

Valvular disease, especially mitral- or aortic, can cause volume and pressure overload of the left ventricle of the heart. This overload causes dilation and / or hypertrophy of the left ventricle which in the long term decreases the pump function.

Dilated cardiomyopathy (DCM) is characterized by dilatation of one or both of the ventricles of the heart, with a general decrease in contractility and consequently a decreased pump function. In about 30% of the cases, DCM is hereditary.

 

Restriction of ventricular filling by a tight (inflammated or constrictive) pericardium or by pericardial effusion and tamponade can be the cause of diastolic HF.  

**ß-blockers

**Disulfiram,

*Hypo- or hyperthyroidism *Cushing syndrome

*Adrenal insufficiencyexcessive growth hormone in acromegaly*Phaeochromocytoma.

===Nutrional status===

*Haemochromatosis *Connective tissue disease.

The therapeutic management of HF involves both pharmacological and non-pharmacological treatment. The goal is reduction in mortality and morbidity, prevention of the progression of HF, and the treatment of (non-)cardiovascular co-morbidities.

Education of both the patient and their family about HF and its symptoms is important. The patient and/or the caregiver should be able to undertake appropriate actions such as adjusting the diuretic dose or contact the physician when necessary. (Class I recommendation, level of evidence C; see table 4) Education on the importance and (side) effects of medication should be provided to the patient in order to increase compliance. (Class I recommendation, level of evidence C)

In patients with severe symptoms of HF, restriction of fluid intake (to 1500 ml/day) may be considered. (Class IIa recommendation, level of evidence C) Also, patients should be educated on salt content of food and minimize intake (< 2 gram/ day) in order to prevent fluid retention. (Class I recommendation, level of evidence C)

CHF patients should carefully monitor their body weight. A sudden increase in weight is a potential consequence of fluid retention and deterioration of HF. When patients notice a weight gain of >2kg in 3 days they should consult a physician. (Class I recommendation, level of evidence C) In obese patients (body mass index of > 30 kg/m²), weight reduction should be promoted to prevent progression of HF, decrease symptoms and improve the overall wellbeing of the patient. (Class IIa recommendation, level of evidence C) Also, attention should be paid to weight loss due to malnutrition which is frequently observed in severe HF. An altered metabolism, inflammatory mechanisms or a decreased food intake may be important factors in the pathophysiology of cardiac cachexia in HF. (Class I recommendation, level of evidence C)

Alcohol intake should be minimized, as it may increase blood pressure and/or have a negative inotropic effect. (Class IIa recommendation, level of evidence C) Smoking cessation should be encouraged. It is recommended that patients with HF receive support and advice on this topic. (Class I recommendation, level of evidence C). A reduction in alcohol and tobacco intake might also improve co-morbidities including sleep disorders.

Exercise training is recommended to all chronic stable HF patients. Twenty years ago, exercise was strongly discouraged in patients with HF as the general conception was that it was harmful. Nowadays, numerous studies have shown the opposite. Rehabilitation programmes have shown to increase exercise capacity and health related quality of life and decrease hospitalization rates and symptoms. (Class I recommendation, level of evidence A)

Other non-pharmacological treatment recommendations include immunization of HF patients (pneumococcal- and influenza vaccination should be considered), the consulting of a physician around pregnancy, the screening for depression and sleep disorders which require additional medical attention.  

A flowchart for treatment of patients presenting with systolic HF is depicted in Figure 5. Medication with a class I indication in patients with systolic heart failure are summarized in Table 5. Indications, mode of action, contraindications of the medication, and possible side effects included in this algorithm are discussed below.

[[Image:management_chronic_systolic_hf.svg|thumb|400px|Figure 5 treatment options for patients with chronic systolic HF]]

===Angiotensin-converting enzyme (ACE) inhibitors===

An ACE inhibitor (in addition to beta blocker) is indicated for every patient with symptomatic systolic HF and an EF≤40 % (NYHA class II-IV). (Class I recommendation, level of evidence A) Contraindications for the use of ACE inhibitors are:

ACE inhibitors relieve the heart by decreasing the preload and afterload. This is achieved through two mechanisms. Firstly, conversion of angiotensin-I to angiotensin–II is inhibited, which reduces vasoconstriction and lowers BP. Secondly, production of aldosterone is decreased, as angiotensin II induces this production. Aldosterone stimulates sodium- and water retention. Possible side effects are symptomatic hypotension (dizziness), hyperkalaemia, worsening renal function and cough.  

In patients with congestive HF, total mortality and hospitalization are significantly reduced by ACE inhibitors <cite>18</cite>.

===ß-Blockers===

ß-Blockade (in addition to an ACE inhibitor or ARB when ACE inhibitor is not tolerated) is indicated for every patient with symptomatic systolic HF and an EF ≤40 % (NYHA class II-IV) and in asymptomatic patients with a LVEF ≤40% after a MI . (Class I recommendation, level of evidence A.)<cite>19</cite>  

*Second- or third degree heart block, sick sinus syndrome, sinus bradycardia

ß-Blockers mainly exert their effect by reducing the toxic effects of the sympathetic nervous stimulation on the heart and by deactivating the renin-angiotensin system.  

In patients with persistent symptoms after treatment with a combination of beta blocker and ACE inhibitor or ARB, an mineralocorticoid/aldosterone receptor antagonist (MRA) is recommended. (Class I recommendation, level of evidence A)

Diuretics reduce preload by venous vasodilatation and by increasing diuresis. As a result, filling pressures of the heart and the lung vasculature decrease . Although the effects of diuretics on mortality and morbidity have not been studied in patients with HF (irrespective of EF), it is recommended in patients with signs and symptoms of congestion as diuretics relieve dyspnoea and oedema. Figure 6 depicts the nephron and sites where different diuretics work.

Loop of Henle diuretics act on the ascending loop of Henle in the kidney tubules to inhibit sodium and chloride (and indirectly calcium and magnesium) reabsorbtion. This will ultimately result in increased urine production of sodium and water. Compared to thiazides, loop diuretics produce a more intense and shorter diuresis.

Thiazide increases urine production by decreasing reabsorbtion of sodium in the distal tubule. This type of diuretic is often used in combination with loop diuretics to enhance their effects, but may be less effective in patients with a severely reduced kidney function.  

Adding this drug is suggested for patients with moderate to severe symptomatic HF (NYHA class II to IV, refer to table 2) and an LVEF < 35%. (Class I recommendation, level of evidence A) Contraindications:

Possible side effects include hyperkalaemia, hyponatremia, worsening renal function, and breast tenderness and/or enlargement. Eplerenon has less mastopathy side effects and is alternative to spironolacton. In patients with severe heart failure, spironolactone in addition to standard therapy, reduces morbidity and mortality <cite>20</cite>.

[[Image:Henle_loop.svg|thumb|400px|Figure 6 diuretics and site of action in the nephron.]]

Patients with heart failure may be treated with a thiazide diuretic, which should be switched to a loop diuretic in case of a suboptimal response. In patients with a decreased renal function, a loop diuretic is the mainstay of treatment. Addition of a thiazide diuretic to a loop diuretic can be considered in case of a suboptimal response of loop diuretic alone, when given in sufficient doses (furosemide 250 mg twice daily), suggesting diuretic resistance because of distal tubular increased activity of retaining sodium. In all patients with NYHA II or more, except in those with a creatinin clearance < 20 ml/min (creatinin > 220 micromol/L), addition of an aldosterone antagonist should be considered . In special cases in which hypercapnia plays a role, metabolic alkalosis can result from diuretics, and acetazolamide, a reversible carbonic anhydrase inhibitor, is then a solution as alternative diuretic.  

ARBs are recommended in patients who do not tolerate an ACE inhibitor. Until recently, addition of ARBs were the first choice recommendation in patients with HF and EF ≤40% who remained symptomatic despite optimal treatment with ACE inhibitor and beta blocker. As aldosteron antagonists have also proven their effects in NYHA class II patients, aldosteron antagonists have become first choice additional therapy after an ACE inhibitor and betablocker. Whether ARBs may still be recommended in this patient group as added therapy after the addition of aldosteron anatagonist, is not known.  

Possible side effects include symptomatic hypotension (dizziness), hyperkalaemia, and a worsening renal function.

In the past digoxin has been standard treatment in HF. Digoxin inhibits sodium-potassium ATPase in the cellmembrane of the myocytes, and by decreasing the sodium extrusion, also inhibits the exchange of calcium out of the cell for sodium into the cell. More calcium remains in the myocyte and increases contractility of the heart. In contrast to other inotropics, digoxin does not increase mortality.   

Digoxin may be considered to reduce HF hospitalization in patients with symptomatic (NYHA class II-IV) systolic HF in sinus rhythm with an EF ≤45% . These patients should also use an ACE inhibitor (or ARB) and an MRA (or ARB) and preferably a beta blocker. (Class IIb recommendation, level of evidence B) This may also be considered in patients with an EF ≤45% and persisting symptoms despite treatment with an ACE inhibitor (or ARB) and an MRA (or ARB). (Class IIb recommendation, level of evidence B)

Possible side effects include sinoatrial or atrioventricular block, arrhythmias or signs of toxicity (nausea and visual effects as halo’s).

Ivabradine lowers heart rate through inhibition of the If channel in the sinus node. This drug can be used in patients who are still in NYHA class II-IV after treatment with ACE inhibitor (or ARB), beta blocker and an MRA (or ARB), who have a LVEF≤35%, are in sinus rhythm and have a heart rate≥75 beats/min. Ivabradine may also be used in patients who do not tolerate, or have contraindications for the use of beta blockers.  

H-ISDN can be used as an alternative treatment when both ACEI and ARBs are not tolerated in symptomatic HF patients with a LVEF≤45% and dilated LV (or EF≤35%). These patients should also receive a beta blocker and MRA. (Class IIb recommendation, level of evidence B). H-ISDN can be used in addition to the standard HF treatments (ACEI, beta blocker and MRA) in patients of Afro-American descent (Class .. recommendation).  H-ISDN may reduce risk of HF hospitalization and risk of premature death in patients with a LVEF≤45% and dilated LV (or EF≤35%)with persisting symptoms despite treatment with beta blocker, ACEI (or ARB), and an MRA (or ARB). (Class IIb recommendation, level of evidence B)

 

===Other===  

When severe symptoms of heart failure quickly develop over time, it is named acute heart failure. In Table 6, common acute HF medications and their recommended doses are summarized. In Figure 7, a flowchart for the treatment of acute HF is depicted. The mainstay of acute heart failure therapy are diuretics, vasodilators, inotropics and vasopressors. Moreover, oxygen and morphine can be added.  

[[Image:acute_hf_flowchart.svg|400px|thumb|Figure 7 flowchart acute HF]]

| colspan="2"|Adequate blood pressure and signs of overfilling

|}

!colspan="3"|Table 7 Medication in chronic heart failure

|1^st week:::6.25mg t.i.d.

|3-5 weeks:::12.5mg t.i.d.

|>7 weeks:::25mg t.i.d.

|1^st week:::5-10mg s.i.d.

|5-7 weeks:::25mg t.i.d.

|>7 weeks:::50 mg t.i.d.

|1^st week:::2.5-5mg b.i.d.

|3-5 weeks:::5-10mg b.i.d.

|>7 weeks:::10-20mg b.i.d.

|1^st week:::50mg s.i.d.

|3-5 weeks:::100mg s.i.d.

|>7 weeks:::100-200mg s.i.d.

|1^st week:::25mg s.i.d.

|3-5 weeks:::50mg s.i.d.

|>7 weeks:::100-200mg s.i.d.

|1^st week:::3.75mg s.i.d.

|3-5 weeks:::5mg s.i.d.

|>7 weeks:::7.5-10mg s.i.d.

|1^st week:::2.5mg s.i.d.

|3-5 weeks:::3.75mg s.i.d.

|>7 weeks:::5-7.5-10mg s.i.d.

|1^st week:::6.25mg b.i.d.

|3-5 weeks:::12.5mg b.i.d.

|>7 weeks:::25mg b.i.d.

|1^st week:::3.125mg b.i.d.

|3-5 weeks:::6.25mg b.i.d.

|>7 weeks:::12.5-25mg b.i.d.

|1^st week:::2.5mg s.i.d.

|3-5 weeks:::5mg s.i.d.

|>7 weeks:::10mg s.i.d.

|1^st week:::2.5mg s.i.d.

|3-5 weeks:::5mg s.i.d.

|>7 weeks:::10mg s.i.d.

|1^st week:::potassium <5.0: 25mg s.i.d.

|potassium 5.0-5.5: 12.5mg s.i.d.

|3rd week:::potassium <5.0: 25mg s.i.d.

|potassium 5.0-5.5: 12.5mg s.i.d.

|Continue with 0.25mg s.i.d.

|3-5 weeks:::8mg s.i.d.

|>7 weeks:::16mg s.i.d.

|3-5 weeks:::160mg s.i.d.

|>7 weeks:::320mg s.i.d.

|Start:::25mg t.i.d.

|3-5 weeks:::50mg t.i.d.

|>7 weeks:::75-100mg t.i.d.

|Start:::20mg b.i.d.

|3-5 weeks:::40mg b.i.d.

|>7 weeks:::80mg b.i.d.

[[Image:CRT_flowchart.svg|thumb|400px|Figure 8 flowchart CRT]]

[[Image:HF_prognosis_trials.svg|thumb|right|400px|Figure 9 Two-year mortality in landmark contemporary clinical heart failure trials (from Cleland et al)]]

Prevention of sudden death is an important goal in HF as approximately half of the deaths occur suddenly and many of these are related to ventricular arrhythmias.  Implantable cardioverter-defibrillator (ICD) therapy is recommended in survivors of cardiac arrest , irrespective of EF, when life expectancy is >1 year. (Class I recommendation, level of evidence A).  

In symptomatic HF patients (NYHA class II-III) with an EF ≤35% after more than 3 months of pharmacological treatment, and a life expectancy >1 year, prophylactic ICD implantation is recommended in patients with ischaemic aetiology (Class I recommendation, level of evidence A) and non-ischeamic aetiology (Class I recommendation, level of evidence B).  

Cardiac resynchronization therapy (CRT) is indicated in patients with symptomatic heart failure with one type and severity of ventricular conduction delay (LBBB, QRS≥120 msec), and preferably in patients with sinus rhythm. The responder rate (improvement of at least 5% EF) is about 70%. Recommendation for use of this therapy differs according to heart rhythm, NYHA class, QRS duration and morphology, and LVEF. This is depicted in the Figure 8.  

Figure 5 offers recommendations to which patients should receive ICD treatment. In this flowchart, the timing of the placement has not been defined completely. In most patients, it should be safe to wait for their ICD whilst receiving (pharmalogical) treatment as events typically occur after 6-12 months. <cite>12</cite> In exception to this rule, in high risk patients (i.e. patients with major myocardial infarction (MI), extensive fibrosis on the MRI or NSVT despite optimal pharmalogical treatment), an ICD implantation should not be postponed too long. Early (within 40 days after event) ICD placement after an acute myocardial infarction has not been shown to reduce mortality, because the patients most at risk of sudden death are also the patients most at risk of death due to heart failure. <cite>13</cite><cite>14</cite><cite>15</cite> For this reason, prophylactic  ICD treatment is recommended only after 40 days in post-infarct patients who have an EF < 35%. For non-ischemic heart failure patients, three months is considered a safe waiting time for an ICD. There are however also higher risk patients among them, and this should be a decision made for every patient individually.<cite>16</cite>

 

When a patient has severe and progressive HF, prognosis is grim. Considering the paucity of donor hearts, the waiting list for a heart transplantation may be long and early consideration of heart transplantation is part of the treatment strategy in HF. Average 2-year survival after cardiac transplantation is approximately 80%. A patient in NYHA class III should already be investigated with an exercise test for maximal oxygen uptake, to consider further steps. Indication for heart transplantation includes a VO2 max < 14 ml/min/kg.<cite>17</cite> Exclusion criteria are pulmonary hypertension (risk of immediate RV donor failure), severe comorbidity, and diabetes mellitus with organ damage.  Left Ventricular Assist Devices are more commonly used as bridge to transplant when on the waiting list. They have evolved from pulsatile to continuous flow pumps, with less complications and a longer durability.  Often Left Ventricular Assist Devices become destination therapy.   

To date, no evidence exists of any treatment reducing morbidity or mortality in this patient group. With the aim to control water and sodium retention and decrease breathlessness and edema, diuretics are prescribed to HFPEF patients. Furthermore, ACE-I, Angiotensin II blockers and/or Betablockers may be considered. The CHARM trial including 3023 HF patients with preserved EF, showed angiotensin II blockade (candesartan) to have a moderate effect on hospital admission but showed no effect on risk of cardiovascular death.<cite>8</cite>

The life expectancy of a patient with heart failure is determined by age, NYHA class, LVEF, normal level of sodium, systolic blood pressure, use of medication and use of ICD or CRT-D (Seattle Heart failure score). The mean yearly annual mortality is about 10%, varying from <6% per year when a normal LVEF is found, to > 14% per year with an EF of < 15%.  

Trials with medication illustrate that the (short term) benefit of medication is highest when the NYHA class is higher (Figure 9).<cite>11</cite>