Right vs. left heart failure Right and left heart failure refers to whether the patient has either pre- dominantly systemic venous congestion (swollen ankles, hepatomegaly) or pulmon ary venous congestion (pulmonary oedema). These terms do not necessarily indicate which ven tricle is most seriously affected. Fluid retention in heart failure is due to a combination of factors: reduced glomerular \201 ltration rate (GFR), and activation of the renin \200\223 angiotensin \200\223aldoster one system, and sympathetic system. However, remember there are causes for swollen ankles o ther than heart failure (gravitational disorder, e.g. immobility, venous thrombosis or obst ruction, varicose veins, hypoproteinaemia, e.g. nephrotic syndrome or liver disease, lympha tic obstruction). High-output vs. low-output heart failure A variety of high-output states may lead to heart failure, e.g. thyrotoxicosis, Paget \200\231s disease, beri-beri, and anemia. This is chara cterized by warm extremities and normal or widened pulse pressure. The arterial \200\223mix ed venous oxygen saturation (a marker of the ability of the heart to deliver oxygen to the metabolizing tissues) is typically normal or even low in high- output heart failure. In con trast, low-output states are characterized by cool pale extremities, cyanosis due to system ic vasoconstriction, and low pulse volume. The arterial \200\223mixed venous oxygen saturat ion is typically abnormally high in low-output states. This page intentionally left blank 372 CHAPTER 7 Heart failure Causes and precipitants In all patients with heart failure, it is important to carefully co nsider the underlying etiology, as there may be speci \201 c exacerbating factors or other diseases that in \202 uence the patients \200\231 management. A non-exhaustive list is gi ven below. Etiology of heart failure \200 Ischaemic heart disease Alcoholic cardiomyopathy \200 Post viral \200 Peripartum cardiomyopathy \200 In \201 ltrative disease (amyloidosis, (accounting for 70 % of patients with heart failure in the developed world) Idiopathic dilated cardiomyopathy (unknown etiology, up to 50 % may be familial) sarcoidosis) Connective tissue disease \200 Iatrogenic (chemotherapy, Valve disease (accounting for 10 % of patients with heart failure) radiotherapy) Infections (Chagas \200\231 disease, human immunode \201 ciency virus (HIV)) \200 Thyroi d disease (severe hypo- or Hypertension (the primary cause of heart failure in patients of African-Caribbean descent) hyperthyroidism) \200 Haemochromatosis \200 Nutritional (beri-beri) Patients with compensated heart failure have a high rate of readmission to hospital with ac ute exacerbations. A number of studies have demon- strated that a precipitating cause for e mergency admission to hospital with heart failure can be identi \201 ed in up to two-third s of patients. \200 Inappropriate reduction in therapy: self-discontinuation or iatrogeni c withdrawal of diuretics, angiotensin-converting enzyme inhibitor (ACE-I), digoxin, as wel l as dietary excess of salt are recognized precipitants. Education of the patient/family is important. Cardiac arrhythmias: most commonly atrial \201 brillation (AF), but any tachyarrhythmia will further reduce LV \201 lling and stroke volume, and may exacerbate i schaemia. Marked bradycardia reduces cardiac output, especially if stroke volume cannot inc rease any further. Myocardial ischaemia or infarction: exacerbates LV dysfunction, and may worsen mitral regur gitation (MR) due to ischaemia of papillary muscles. Infection: respiratory infections are more common, but any systemic sepsis can precipitate heart failure due to a combination of factors such as direct myocard ial depression from in \202 ammatory cytokines, sinus tachycardia, fever, etc. Anemia: this causes a high-output state that may precipitate acute heart failure, and may exacerbate underlying ischaemia. Concomitant drug therapy: drugs that directly depress myocardial function (e.g. calcium ant agonists \200\224 verapamil, diltiazem; many antiarrhythmics, anesthetics, over-enthusiast ic initiation of B -blockers, etc.), as well as drugs causing salt and water retention (e.g . non-steroidal anti- in \202 ammatory drugs (NSAIDs), oestrogens, steroids, COX-2 antagon ists) may precipitate heart failure. CAUSES AND PRECIPITANTS 373 Alcohol: this is directly toxic and, in excess, can depress myocardial function as well as predispose to arrhythmias. Pulmonary embolism: the risk increases in the immobile patient with low-output state and AF. It is very important to look for precipitating causes in all patients with heart failure. O nce the precipitant has been identi \201 ed and treated, appropriate measures (patient and family/education, adjustment of therapy, etc) should be put into place to prevent recurren ce. See Table 7.1. Table 7.1 Population-attributable risk of heart failure related to various risk factors a Risk factor Attributable risk ( % ) Coronary disease 61.6 Cigarette smoking 17.1 Hypertension 10.1 Physical inactivity 9.2 Male sex 8.9 <High school education 8.9 Overweight 80 Diabetes 3.1 Valvular heart disease 2.2 a He, J, Ogden LG, Bazzano LA, et al (2001). Risk factors for congestive heart failure in U S men and women: NHANES 1 Epidemiologic follow-up study. Arch Intern Med 161 : 996. Conditions mimicking heart failure \200 Obesity \200 Chest disease \200\224 including lung, Intrinsic renal disease \200 Intrinsic hepatic disease \200 Pulmonary embolic disease \200 Depression and/or anxiety diaphragm, or chest wall Venous insuf \201 ciency in lower limbs. \200 Drug-induced ankle swelling (e.g. dihydrop yridine calcium blockers) disorders Severe anemia \200 Thyroid disease \200 Bilateral renal artery stenosis Drug-induced \202 uid retention (e.g. NSAIDs) \200 Hypoalbuminaemia 374 CHAPTER 7 Heart failure Signs and symptoms The evaluation of a heart failure patient should start with a comprehens ive history and clinical examination. Primary symptoms can be attributed to either reduced cardiac output or \202 uid accumulation, and include: \200 fatigue \200 dyspnoea (on exertion or at palpitations (tachycardia) \200 hypotension \200 raised jugular venous pressure (JVP) \200 displaced apex beat \200 gallop rhythm (3rd heart sound) \200 cahexia. rest) orthopnoea \200 paroxysmal noctural dyspnoea \200 peripheral oedema \200 chest pain It is important to remember that heart failure is a multisystem disorder affecting every si ngle aspect of a patient \200\231s body. It is not unusual for patients to present with: \200 gastrointestinal symptoms secondary to congestive hepatomegaly, ascites, reduced bowel perfusion, and oedema (abdominal distension and pain, anorexia, bloa ting, nausea, constipation, jaundice) \200 genitourinary symptoms secondary to impaired r enal perfusion (oliguria/anuria, urinary frequency, nocturia) cerebrovascular symptoms secondary to cerebral hypoperfusion and associated electrolyte abn ormalities (confusion, memory impairment, anxiety, headaches, insomnia, bad dreams or night mares, psychosis with disorientation, delirium, or hallucinations) musculoskeletal symptoms (gout, carpal tunnel syndrome, muscle cramps). Many of these signs can be dif \201 cult to elicit particularly in a noisy emer- gency or outpatient clinic. Even in study conditions, the reproducibility and inter-observer agreement of the presence of signs is low. Despite this, a clinical diagnosis of heart failure can be made with some certainty when multiple signs are present in the same patient (see Table 7.2 ). Symptoms alone can be used to classify the severity of congestive heart failure (CHF) and t o monitor the effect of treatment, although the link between symptoms and degree of LV dysf unction is weak. The New York Heart Association classi \201 cation (NYHA) is widely used. NYHA classi \201 cation of heart failure No limitation of physical activity. Class I Sligh t limitation of physical activity \200\224 symptoms with ordinary Class II levels of exert ion (e.g. walking up stairs). Marked limitation of physical activity \200\224 symptoms wit h minimal levels of exertion (e.g. dressing). Class III Class IV Symptoms at rest. SIGNS AND SYMPTOMS 375 An alternative classi \201 cation system of heart failure is the \200\230Stages of Heart Failure \200\231 proposed by the American College of Cardiology (ACC) and the American Hear t Association (AHA). This classi \201 cation system places particular emphasis on the prog ressive nature of the heart failure, and de \201 nes the appropriate therapeutic approach for each stage (see Table 7.2). Unlike the NYHA classi \201 cation, this system is unidire ctional and therefore cannot be used as a means of assessing the patient \200\231s response to treatment. See also Fig. 7.2. Table 7.2 ACC/AHA stages of heart failure Stage A Stage B Stage C Stage D Refractory HF symptoms despite maximal medical therapy Structural or functional heart disease with current or prior symptoms or signs of HF Structural or functional heart disease but without symptoms or signs of HF At high risk for developing heart failure (HF) but without identi \201 ed structural or fu nctional heart disease, symptoms or signs of HF e.g. marked symptoms on minimal exertion or at rest, hospitalized patients e.g. known structural heart disease with associated dyspnoea, fatigue, oedema e.g. previous MI, left ventricular hypertrophy, reduced EF, valvular lesions e.g. patients with: hypertension, atherosclerosis, diabetes, obesity, metabolic syndrome 376 CHAPTER 7 Heart failure Suspected heart failure because of history, symptoms, and signs. Seek to exclude heart failure through: Other recommended tests: (mostly to exclude other conditions) 12-lead ECG \200 and/or natriuretic peptides (BNP or NTproBNP) \200\223where available. chest X-ray \200 blood tests: U&Es, creatinine, FBC, TFTs, LFTs, glucose, and lipids \200 urinalysis, peak flow or spirometry. One or more abnormal Both normal Heart failure unlikely. Consider alternative diagnosis. Imaging by echocardiography* No abnormality detected Heart failure unlikely, but if diagnostic doubt persists consider d iastolic dysfunction and consider referral for specialist assessment. Abnormal Assess HF severity, etiology, precipitating and exacerbating factors, and type of cardiac dysfunction. Correctable causes must be identified. Consider referral. Fig. 7.2 Algorithm summarizing recommendations for the diagnosis of heart failure. *Alterna tive methods of imaging the heart should be considered when a poor image is produced by tra nsthoracic Doppler 2D-echocardiography \200\224 alternatives include transoesophageal echo cardiography (TOE), radionuclide imaging, or cardiac magnetic resonance imaging (MRI). BNP = B-type natriuretic peptide; ECG = electrocardiogram; FBC = full blood count; LFTs = l iver function tests; NTproBNP = N-terminal pro-B-type natriuretic peptide; TFTs = thyroid f unction tests; U&Es = urea and electrolytes. This page intentionally left blank 378 CHAPTER 7 Heart failure Investigations Investigations for all patients with heart failure \200 ECG : although the re are no speci \201 c changes in heart failure, a normal ECG is observed in only 2 % of cases and should encourage the clinician to consider an alte rnative diagnosis in the absence of \201 rm clinical signs. Common \201 ndings include: sinus tachycardia/bradycardia, arrhythmias, voltage criteria for left ventricular hypertro phy (LVH), evidence of current or past ischaemia/infarction, and conduction system defects. \200 Chest X-ray (CXR): permits assessment of pulmonary congestion and may demonstrate o ther non-cardiac causes of dyspnoea. Common \201 ndings include: cardiomegaly, pulmonary congestion with alveolar oedema, prominent upper lobe vessels, \200\230bat \200\231s wings \200\231 and Kerley B lines and pleural effusions (see Fig. 7.3 ). Echocardiography (ECHO): this is the key investigation in patients with HF and is mandatory for con \201 rming the diagnosis. Apart from documenting systolic and diastolic left ventricular function, the scan is useful in the identi \201 cation of various causes or complications of heart failure (see Table 7.3 ). If an echocardiogram doe s not con \201 rm a diagnosis of HF despite suggestive clinical symptoms and signs, consid er an alternative diagnosis or a referral for a specialist review. Natriuretic peptides : evidence exists supporting the use of plasma concentrations of natri uretic peptides for diagnosing, staging, or even identifying patients at risk for clinical events. A normal plasma concentration in an untreated patient has a high negative predictiv e value, making HF an unlikely cause of symptoms. \200 Blood tests : FBC, U&Es, LFTs, TFT s, glucose, uric acid. Investigations to consider for selected patients with heart failure \200 Blood tests: tro ponin I or T, iron studies, folate, vitamin B 12 , autoimmune screen, immunoglobulins and protein electrophresis, serum ACE \200 Viral titre s \200 Urine sample: albumin/creatinine ratio, 24-hour urine collection for protein, catecholamines, Bence \200\223Jones protein Arterial blood gasses \200 Pulmonary function tests \200 Exercise testing \200 Ambula tory ECG monitoring (QT dispersion, heart-rate variability) \200 Stress imaging \200 Ra dionucleotide ventriculography \200 Cardiac magnetic resonance \200 Coronary angiograph y (computed tomography (CT) or conventional) \200 Myocardial biopsy \200 Right-heart ca theterization. INVESTIGATIONS 379 Table 7.3 Conditions predisposing to or complicating heart failure that may be identi \201 ed by echocardiography Echocardiographic \201 ndings Examples of possible etiology Identi \201 cation of anatomical defects Atrial septal defect (ASD), ventricular septal defect (VSD) Valvular pathology Aortic valve or mitral valve stenosis or insuf \201 ciency Pericardial disease Acute or chronic pericarditis Constrictive pericarditis Pericardial effusion Ischaemic heart disease Identi \201 cation of regional ventricular wall motion abnormalities Altered myocardial architecture Hypertrophic cardiomyopathy In \201 ltrative diseases (amyloidosis) Estimation of pulmonary artery pressure Pulmonary hypertension (cor pulmonale as a result of primary pulmonary hypertension or seco ndary to lung disease) Identifying complications of reduced ventricular function Intramural thrombus secondary to ventricular dilatation, reduced contraction, or aneurysm 380 CHAPTER 7 Heart failure (a) (b) Fig. 7.3 CXR \201 ndings in heart failure. (a) There is cardiomegaly with prominent upper lobe vessels and alveolar oedema ( \200\230Bat \200\231s wing shadowing \200\231); (b) mag ni \201 cation of the right costophrenic angle showing septal lines (Kerley B lines) due t o interstitial oedema. This page intentionally left blank 382 CHAPTER 7 Heart failure Management of heart failure Management outline in chronic heart failure \200 Establish a \201 rm diagnosis of HF \200 Attempt to determine the etiology and ascertain the severi ty of HF \200 Correct precipitating or exacerbating factors \200 Multidisciplinary appr oach to treatment (HF is a complex syndrome necessitating the involvement of a number of healthcare professionals in the community and secondary care including: general practiitoner (GP), cardiologist, electrophysiologist, car diac surgeon, heart failure nurse, cardiac rehabilitation team, dietician, psychologist, ex pert in sexual dysfunction) Education of the patient and relatives (see Table 7.4 ) \200 Monitor progress and manage accordingly. Objectives of treatment \200 Reduce mortality \200 Reduce morbidity (to improve quality of life by relieving symptoms, increasing exercise capacity, reducing the need for hospitalization and providing end-of-li fe care) Prevention (can be divided into two separate entities: (1) prevention of cardiovascular ris k factors that may lead or contribute to the development of heart failure, i.e. hypertensio n, diabetes, obesity, and (2) prevention of progression of myocardial damage, remodeling, a nd reoccurrence of symptoms once HF is established). Fig 7.4 summarizes a treatment algorithm for patients with symptomatic HF and reduced systo lic function. Table 7.4 Essential topics in patient education with associated skills and appropriate self -care behaviors Educational topics Skills and self-care behaviors De \201 nition and etiology of heart failure Understand the cause of heart failure and why symptoms occur Symptoms and signs of heart failure Monitor and recognize signs and symptoms Record daily weight and recognize rapid weight gai n Know how and when to notify healthcare provider Use \202 exible diuretic therapy if app ropriate Pharmacological treatment Understand indications, dosing, and effects of drugs Recognize the common side-effects of e ach drug Risk-factor modi \201 cation Understand the importance of smoking cessation Monitor blood pressure if hypertensive Maint ain good glucose control if patient has diabetes Avoid obesity Diet recommendation Sodium restriction if prescribed Avoid excessive \202 uid intake Modest intake of alcohol Monitor and prevent malnutrition MANAGEMENT OF HEART FAILURE 383 Table 7.4 (contd.) Educational topics Skills and self-care behaviors Exercise recommendation Be reassured, comfortable about physical activity Understand the bene \201 ts of exercise Perform exercise training regularly Sexual activity Discuss problems with healthcare professionals Be reassured about engaging in sexual interc ourse and understand speci \201 c sexual problems and various coping strategies Immunization Receive immunization against infections such as in \202 uenza and pneumococcal disease Sleep and breathing disorders Recognize preventive behavior such as reducing weight in obese, smoking cessation, abstinen ce from alcohol Learn about treatment options if appropriate Adherence Understand the importance of following treatment recommendations Maintain motivation to fol low treatment plan Psychosocial aspects Understand that depressive symptoms and cognitive dysfunction are common in patients with H F, and the importance of social support Learn about treatment options if appropriate Prognosis Understand important prognostic factors and make realistic decisions Seek psychosocial supp ort if appropriate ESC guidelines for the diagnosis and treatment of acute and chronic heart failure (2008). E ur Heart J 29 : 2388 \200\2232442. 384 CHAPTER 7 Heart failure Symptomatic heart failure with reduced systolic function Diuretic (loop/thiazide) + ACE-I (or ARB) + -blocker Persisting symptoms and signs? No Yes Add aldosterone antagonist if aldosterone antagonist is contraindicated/not tolerated consi der ARB on top of the ACE-I Persisting symptoms? No Yes QRS >120 ms? LVEF <35%? No No Yes Yes Consider CRT-P or CRT-D Consider: digoxin, hydralazine/nitrates Consider ICD No further treatment Consider referral for: LVAD, transplantation Palliation Fig. 7.4 Treatment algorithm for patients with symptomatic heart failure and reduced systol ic function. Adapted from ESC (2008). Guidelines for the diagnosis and treatment of acute a nd chronic heart failure. Eur Heart J 29 : 2388 \200\2232442 and NICE guidelines Y www.nice .org . ARB = angiotensin receptor blocker; LVAD = left ventricular assist device. This page intentionally left blank 386 CHAPTER 7 Heart failure Diuretics in heart failure \200 Diuretics provide symptomatic relief from pulmonary and s ystemic congestion by reducing \202 uid overload. With the exception of aldosterone antagonists (spironalactone and eplerenone), diuretics do not offer any signi \201 cant prognostic bene \201 t. \200 Loop diuretics cause more p ronounced diuresis (and natriuresis), and are the option of choice in patients with moderat e to severe heart failure. \200 A thiazide may be used in combination with loop diuretics for resistant oedema. Regular monitoring is required to avoid dehydration, hyponatraemia, hypokalaemia, a nd hypomagnesimia. Diuretics cause activation of the renin \200\223angiotensin \200\223aldosterone system and should be used in combination with an ACE-I/ARB when possible. Start with a low dose (especially in diuretic-naive patients and the elderly) and increase the dose until clinical improvement occurs. \200 Once \202 uid overload resolves, readj ust the diuretic dose to avoid dehydration. Aim to maintain \200\230dry weight \200\231 with the lowest dose possible. \200 Self-adjustment of the diuretic dose based on daily weight measurements and other cli nical signs of \202 uid retention should be part of the patient education. It is essential to monitor potassium, sodium, and creatinine levels during diuretic therapy. Practical considerations in the treatment of heart failure with loop diuretics See Table 7. 5 . Table 7.5 Considerations in the treatment of heart failure with loop diuretics Problems Suggested action Increase ACE-I/ARB dosage \200 Add aldosterone antagonist \200 Potassium supplements \200 Magnesium supplements Hypokalaemia/ hypomagnesaemia Fluid restriction \200 Stop thiazide diuretic or switch to loop diuretic \200 Reduce do se/stop loop diuretics if possible \200 Consider arginine vasopressin (AVP) antagonist if available \200 Intravenous (IV) inotropic support \200 Consider ultra \201 ltration Hyponatraemia Consider allopurinol \200 For symptomatic gout use colchicine for pain relief \200 Avoi d NSAIDs Hyperuricaemia/ Gout Assess volume status \200 Consider reduction of diuretic dosage Hypovolaemia/ dehydration DIURETICS IN HEART FAILURE 387 Table 7.5 (contd.) Problems Suggested action Check compliance, \202 uid and salt intake \200 Review other drugs (NSAIDs, steroids) \200 Increase dose of diuretic \200 Consider switching from furosemide to bumetanide or Insuf \201 cient response or diuretic resistance torasemide Add aldosterone antagonist \200 Combine loop diuretic and thiazide/metolazone \200 Admi nister loop diuretic twice daily or on empty stomach \200 Consider short-term IV infusion of loop diuretic \200 Consider low-dose dopamine infusion Check for hypovolaemia/dehydration \200 Exclude use of other nephrotoxic agents, e.g. NSA IDs, Renal failure (excessive rise in urea and/or creatinine) trimethoprim Withhold aldosterone antagonist \200 If using concomitant loop and thiazide diuretic stop thiazide diuretic Consider reducing dose of ACE-I/ARB \200 Consider ultra \201 ltration Adapted from ESC (2008). Guidelines for the diagnosis and treatment of acute and chronic he art failure. Eur Heart J 29 : 2388 \200\2232442. 388 CHAPTER 7 Heart failure Diuretic doses used in patients with heart failure See Table 7.6 . Table 7.6 Diuretic doses used in patients with heart failure Diuretics Initial dose (mg) Usual daily dose (mg) Loop diuretics a Furosemide 20 \200\22340 40 \200\223240 Bumetanide 0.5 \200\2231.0 1 \200\2235 Torasemide 5 \200\22310 10 \200\22320 Thiazides b Bendro \202 umethiazide 2.5 2.5 \200\22310 Hydrochlorothiazide 25 25 \200\223100 Metolazone 2.5 2.5 \200\22310 Indapamide 2.5 2.5 \200\2235 Potassium-sparing diuretics c Spironolactone/eplerenone 12.5 \200\22325 50 Amiloride 2.5 5 \200\22320 Triamterene 25 50 Adapted from ESC (2008). Guidelines for the diagnosis and treatment of acute and chronic he art failure. Eur Heart J 29 : 2388 \200\223442. a Higher doses may be required in individua ls with renal impairment; excessive doses however may cause renal impairment and ototoxicit y. b Do not use thiazides if estimated GFR (eGFR)<30 mL/min, except when prescribed synergi stically with loop diuretics. c Aldosterone antagonists should always be preferred to other potassium-sparing diuretics. This page intentionally left blank 390 CHAPTER 7 Heart failure Angiotensin-converting enzyme inhibitors for heart failure Unless contraindicated or not to lerated, all patients with symptomatic HF or asymptomatic left ventricular dysfunction (LVE F \211 40 % ) should receive an ACE-I ACE-Is reduce mortality and morbidity (improve symp toms, exercise tol- erance, and quality of life, and reduce the need for hospitalization) a nd improve or at least prevent further deterioration of ventricular function. Contraindications \200 History of angioedema \200 Bilateral renal artery stenosis \200 Serum potassium concentration > 5 mmol/L \200 Serum creatinine > 220 mol/L \200 Sev ere aortic valve stenosis. Initiation of ACE inhibitors \200 Check renal function and serum electrolytes. \200 Sta rt with a low dose and recheck renal function and serum electrolytes within 1 \200\2232 wee ks of commencing the treatment. Consider dose up-titration at 2 \200\2234-week intervals and recheck renal function and serum electrolytes within 1 \200\2232 weeks of dose uptitration. \200 More r apid dose up-titration can be carried out, but close supervision is required. Once a maintenance dose has been achieved, recheck renal function and serum electrolytes at 1, 3, 6 months, and 6 monthly thereafter. \200 Aim for evidence-based target dose or the maximum tolerated dose. Doses of ACE inhibitors used in heart failure See Table 7.7 . Table 7.7 Doses of ACE-Is used in heart failure Licensed ACE-I Initiating dose (mg) Target dose (mg) Captopril 6.25 three times daily 50 \200\223100 three times daily Cilazapril 0.5 once daily 1 \200\2232.5 once daily Enalapril 2.5 once daily 10 \200\22320 twice daily Fosinopril 10 once daily 40 once daily Lisinopril 2.5 \200\2235.0 once daily 20 \200\22335 once daily Perindopril 2.0 once daily 4 once daily Quinapril 2.5 once daily 10 \200\22320 once daily Ramipril 1.25 once daily 10 once daily (or 5 twice daily) Trandolapril 0.5 once daily 4 once daily ANGIOTENSIN-CONVERTING ENZYME INHIBITORS 391 Practical considerations in treatment of heart failure with ACE inhibitors Deteriorating re nal function \200 Some rise in urea and creatinine is expected and should not cause conce rn. \200 An increase of \211 50 % from baseline or to an absolute concentration of 265 mol/L, whichever is lower, is acceptable. \200 Check for other nephrotoxic drugs (N SAIDs). \200 If creatinine rises to > 265 mol/L but is <310 mol/L, halve the dose of ACE-I and monitor biochemistry closely. If creatinine rises to \211 310 mol/L, stop ACE-I and monitor biochemistry closely. Hyperkalaemia \200 Check for other drugs causing hyperkalaemia (potassium-sparing diuretics, supplements). If potassium rises to > 5.5 mmol/L, halve dose of ACE-I and monitor biochemistry. If potassium rises to > 6.0 mmol/L, stop ACE-I and monitor biochemistry. Symptomatic hypote nsion \200 Asymptomatic hypotension does not require intervention. \200 May improve wit h time. \200 Consider giving dose at night. \200 Consider reducing the dose of other hy potensive drugs (particularly vasodilators). If symptoms persist, reduce (or as a last resort stop) the ACE-I dose and monitor the patient. Cough \200 Consider alternative causes, i.e. deteriorating HF with pulmonary oedema, lung disease. If troublesome, switch to an ARB. Angioedema \200 Discontinue. \200 Consider trial of a n ARB, although angioedema has also been reported with some ARBs. Advice to patients \200 Explain expected bene \201 ts. \200 Treatment is given to impr ove symptoms, to prevent worsening of HF, and to increase survival. Symptoms improve within a few weeks to a few months. \200 Advise patients to report princ ipal adverse effects, i.e. dizziness/ symptomatic hypotension, cough. 392 CHAPTER 7 Heart failure Angiotensin II receptor antagonists for heart failure \200 Angiotensin II receptor blocke rs should be used in patients with heart failure or asymptomatic left ventricular systolic dysfunction (LVEF \211 40 % ) when an ACE-I is not tolerated (cough). As with ACE-Is, ARBs reduce mortality and morbidity (improve symptoms, exercise tolerance, and quality of life, and reduce the need for hospitalization) and improve or at least preve nt further deterioration of ventricular function. Initial studies (Val-HeFT (Valsartan Heart Failure Trial)), CHARM- Added (Candesartan in He art Failure \200\224 Assessment of Mortality and Morbidity)) suggested an added bene \201 t in mortality and risk of hospitalization for deteriorating HF with the combination of AC E-I and ARB compared to either agent alone. A recent study (ONTARGET (Ongoing Telmisartan A lone and in combination with Rampril) however, demonstrated worse major renal outcomes (com posite of dialysis, doubling of serum creatinine, and death) with a combination of ramipril and telmisartan compared to either treatment alone, raising concerns. Currently the addition of an ARB on top of optimal ACE-I treatment should be considered in HF patients who remain symptomatic despite optimal doses of ACE-I and B -blocker, when aldo sterone antagonists are either not tolerated or contraindicated. Contraindications: as with ACE-Is, with the exception of angioedema. \200 Initiation as w ith ACE-Is. \200 Practical considerations as with ACE-Is, with the exception of cough. Doses of angiotensin II receptor blockers used in heart failure See Table 7.8 Table 7.8 Doses of ARBs used in heart failure Licensed ARB Initiating dose (mg) Target dose (mg) Candesartan 4 once daily 32 once daily Losartan 12.5 once daily 100 once daily Valsartan 40 twice daily 160 twice daily This page intentionally left blank 394 CHAPTER 7 Heart failure Beta-blockers for heart failure \200 Unless contraindicated or not tolerated, all patient s with symptomatic heart failure or asymptomatic left ventricular dysfunction (LVEF \211 40 % ) should receive a B -blocker. B -blockers reduce mortality and morbidity (improve symptoms, exercise tolerance, and quali ty of life, and reduce the need for hospitalization) and improve or at least prevent furthe r deterioration of ventricular function. Where possible, B -blockers should be cautiously initiated prior to hospital discharge. Clo se monitoring is required as there may be an initial deterioration in HF symptoms. Contraindications \200 Asthma is not an absolute contraindication given that B -blockers licensed for use in heart failure are highly cardioselective. We would recommend however, t hat they are initiated under a specialist \200\231s supervision after a trial with short-ac ting metoprolol while monitoring peak expiratory \202 ow rate (PEFR) and oxygen saturatio n in a clinical setting with resuscitation facilities. Not recommended in patients with severe asthma and regular exacerbations. In contrast to popular belief, chronic obstructive pulmonary disease (COPD) is not a contra indication to the use of B -blockers in HF patients. Lung function tests with assessment fo r reversible airways obstruction using B -agonists (salbutamol) or antimuscarinics (ipratro pium) may prove a useful adjunct. If signi \201 cant reversibility exists, re-evaluate the COPD diagnosis and perform a trial with a short-acting B -blocker. Second- or third-degree heart block, sick sinus syndrome (in the absence of a permanent pacemaker). Sinus bradycardia (<50 bpm). Initiation of a B -blocker \200 The common practice of addin g a B -blocker to a regime containing an ACE-I is based on the fact that the ACE-I trials w ere performed \201 rst, with the B -blocker trials done with the drugs used on top of the ACE-I. Two large trials however (CARMEN (Randomized Controlled Multicentre Trial), CIBIS I II (Cardiac Insuf \201 ciency Bisoprolol Study)), indicate that the two approaches, i.e. B -blocker \201 rst vs. ACE-I \201 rst, are comparable, thereby allowing clinicians to s elect the best approach for their patients with chronic HF. More importantly, the results o f these studies support a therapeutic strategy in which the institution of an early combina tion therapy should not be delayed. HF symptoms should be relatively stable prior to initiation. \200 Start with a low dose a nd up-titrate every 2 \200\2234 weeks. \200 Monitor the patient for symptoms and signs of deteriorating HF, hypotension, or excessive bradycardia. Aim for the evidence-based target dose or the maximum tolerated dose. BETA-BLOCKERS FOR HEART FAILURE 395 Practical considerations in treatment of heart failure with B -blockers Deteriorating sympt oms and/or signs of HF \200 Exclude co-existent pathology, i.e. increasing breathlessness secondary to bronchospasm in asthma. Remember that fatigue can be a direct side-effect of the B -blocker not related to the HF status. Increase the dose of diuretics (usually required temporarily). \200 If symptoms persist, consider reducing (or as a last resort stopping) the B -blocker dose and monitor the patient. Symptomatic hypotension \200 Asymptomatic hypotension does not require intervention. \200 May improve with time. \200 Consider reducing the dose of other hypotensive drugs ( particularly vasodilators). If symptoms persist consider reducing (or as a last resort stopping) the B -blocker dose and monitor the patient. Excessive bradycardia \200 Perform an ECG and/or ambulatory monitoring when necessary to exclude signi \201 cant heart block, pauses. If heart rate is <50 bpm and the patient is symptomatic, discontinue other contributing drugs (digoxin, amiodarone). If symptoms persist, consider reducing (or as a last resort stopping) the B -blocker dose, and monitor the patient. Sexual dysfunction \200 May be precipitated or exacerbated by B -blockers. \200 Conside r reducing the B -blocker dose. \200 Refer to a specialist. Doses of B -blockers used in heart failure See Table 7.9 . Table 7.9 Doses of B -blockers used in heart failure Licensed B -blocker Initiating dose (mg) Target dose (mg) Bisoprolol 1.25 once daily 10 once daily Carvedilol 3.125 twice daily 25 \200\22350 twice daily Metoprolol succinate a 12.5 once daily 200 once daily Nebivolol 1.25 once daily 10 once daily a Not available in the UK. 396 CHAPTER 7 Heart failure Advice to patients \200 Explain the expected bene \201 ts. \200 Emphasize that treatme nt is given as much to prevent worsening of HF as to improve symptoms; beta-blockers also increase survival. If symptomatic improvement occurs, this may develop slowly \200\224 over 3 \200\2236 months or longer. Temporary symptomatic deterioration may occur (estimated 20 \200\22330 % of cases) during initiation/up-titration phase. Advise the patient to report deterioration and that deterioration (tiredness, fatigue, breathlessness) can usually be easily managed by adjustment of their m edication; patients should be advised not to stop B-blocker therapy without consulting thei r physician. Patients should be encouraged to weigh themselves daily (after walking, before dressing, after voiding, before eating) and to consult their doctor if they have per sistent weight gain. This page intentionally left blank 398 CHAPTER 7 Heart failure Aldosterone receptor antagonists in heart failure \200 Aldosterone antagonists are indica ted in patients with left ventricular dysfunction (LVEF \211 35 % ) and severe symptomati c heart failure (NYHA class III or IV), despite treatment with optimal doses of ACE-I and B -blocker. Aldosterone inhibitors reduce both mortality and the number of hospital admissions secondar y to deteriorating HF symptoms. \200 The \201 rst-line aldosterone antagonist used in c linical practice is spironalactone (RALES (Randomized Aldactone Evaluation Study)). Eplerenone is indicated in a speci \201 c subgroup of post acute MI patients with LVEF \211 40 % and HF or diabetes (EPHESUS (Epelerenone Post- Acute Myocardial Infarction Heart Failure Ef \201 cacy and Su rvival Study)) or in those developing endocrine side-effects on spironalactone (10 % of mal es may develop breast tenderness or enlargement). Contraindications \200 Serum potassium > 5.0 mmol/L \200 Serum creatinine > 220 mol/L \200 Addition to a combination of ACE-I and ARB. Initiation of aldosterone antagonists \200 Check renal function and serum electrolytes. \200 Recheck renal function and serum electrolytes 1 and 4 weeks after starting treatment. Consider dose up-titration after 4 \200\2238 weeks. Do not increase the dose if there is wo rsening renal function or hyperkalaemia. Recheck renal function and serum electrolytes 1 an d 4 weeks after increasing the dose. Aim for the evidence-based target dose or maximum tolerated dose. \200 Recheck renal func tion and serum electrolytes 1, 2, 3, and 6 months after achieving the maintenance dose, and 6 monthly thereafter. Doses of aldosterone receptor antagonists used in heart failure See Table 7.10. Table 7.10 Doses of aldosterone receptor antagonists used in heart failure Licensed aldosterone antagonist Initiating dose (mg) Target dose (mg) Spironalactone 25 once daily 50 once daily Eplerenone 25 once daily 50 once daily ALDOSTERONE RECEPTOR ANTAGONISTS IN HEART FAILURE 399 Practical considerations in treatment of heart failure with aldosterone receptor antagonist s Deteriorating renal function \200 Check for other nephrotoxic drugs (NSAIDs). \200 If creatinine rises to > 210 mol/L, halve the dose of aldosterone antagonist and monitor biochemistry closely. If creatinine rises to \211 310 mol/L, stop the aldosterone antagonist and monitor biochemistry closely. Hyperkalaemia \200 Check for other drugs causing hyperkalaemia (potassium-sparing diuretics, supplements). If potassium rises to > 5.5 mmol/L, halve the dose of aldosterone antagonist and monitor biochemistry. If potassium rises to > 6.0 mmol/L, stop the aldosterone antagonist and monitor biochemistry. Speci \201 c treatment of hyperkalaemia may be needed. Symptomatic hypotension \200 Asym ptomatic hypotension does not require intervention. \200 It may improve with time. \200 Consider reducing the dose of other hypotensive drugs (particularly vasodilators). If symptoms persist, reduce the dose or stop the aldosterone antagonist and monitor the patient. Breast tenderness or enlargement \200 Switch from spironalactone to eplerenone. Advice to patients \200 Explain the expected bene \201 ts. \200 Treatment is given to improve symptoms, prevent worsening of HF, and increase survival. Symptom improvement occurs within a few weeks to a few months of starting treatment. Aviod NSAIDs not prescribed by a physician (self-purchased \200\230over-the - counter \200\231 treatment, e.g. ibuprofen). Temporarily stop sprionolactone if the patient has diarrhea and/or vomiting, and contact the physician. 400 CHAPTER 7 Heart failure Cardiac glycosides (digoxin) in heart failure \200 Digoxin is a useful aid to B -blockers for rate control of AF (when > 80 bpm at rest or > 110 \200\223120 bpm at exercise) in patients with HF, but its role is less well established in patients with sinus rhythm or rate- controlled AF.