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Management of Heart Failure in 2014 Dr CJ Whelan MD FRCP Consultant Cardiologist and Honorary Senior Lecturer Royal Free London NHS Foundation Trust DIAGNOSIS Chronic heart failure A complex syndrome that can result from any structural or functional cardiac disorder that impairs the pumping ability of the heart HF Clinic Patient RS is a 69 yr old gentleman recently referred to the HF team. He has a history of LV dysfunction with an EF of 20% due to IHD. He has had recent multiple admissions to hospital with worsening symptoms NYHA IV. He is now in NYHA III With PND, orthopnoea and pitting oedema to his knees He has LBBB on his ECG with a QRS of 160 ms Medication During last admission beta blocker has been stopped due to symptomatic bradycardia. ACE I has been reduced due to worsening renal function and symptomatic hypotension. Spironolactone has been reduced due to hyperkalaemia Further Management What next? Treatment After discussion at the HF MDT, referred for Biventricular PPM (CRT) with ICD. He was brought into a pre assessment clinic and assessed and counselled by the HF nurse. He was admitted for CRT-D the next week 6 months later RS was followed up in the nurse Led HF clinic 2-4 weekly for assessment and titration of medication. Beta Blocker was reinstated and he is now tolerating 10 mg Bisoprolol. His ACE I was reintroduced and slowly titrated - now on 5mg Ramipril He is tolerating 50 mg Spironolactone His renal function is normal He is biventricular paced He is in NYHA II An echo was repeated showing an improvement with EF 35-40% He attends a cardiac rehab exercise class regularly He has not been admitted to hospital since his CRT-D was implanted Case 2 ED is a 67 yr old gentleman admitted to the medical ward with a history of breathlessness and bilateral ankle oedema. He has had a reduction in exercise tolerance over the last three months and has experienced PND and orthopnoea for a few days prior to admission. Past Medical History STEMI 2008 PPCI to LAD 2008 HTN Hyperlipidaemia Arthritis Drugs on admission Atenolol 25 mg od Perindopril 2 mg od Simvastatin 40 mg od Aspirin 75 mg od Piroxicam 20mg od Social His wife has recently died and he now lives alone. He is retired He has two grown up daughters living in Manchester and Scotland. He drinks up to 5 pints of beer every Friday and Saturday night. He eats mainly microwave meals He is a current smoker of 5 cigarettes per day for 50 yrs. Observations BP 160/90 mmHg HR 100bpm reg Sinus Rhythm Respirations 22/min Bilateral basal creps Third heart sound His ECG shows SR with anterior q waves His Chest x Ray shows Pulmonary oedema Further Findings NT proBNP is raised on admission at 560pmol/L Echo carried out the day after admission shows impaired LV systolic function with an EF of 20% and severe AS He is referred to the HF team. HF Review He is assessed the next day. Diagnosis LV dysfunction due to IHD and severe AS Stop Piroxicam PLAN: Change Atenolol to Bisoprolol 2.5 mg titrating up as tolerated, aim for a resting HR of <70 bpm Commence Furosemide Commence Spironolactone 12.5 mg titrating up to maximum tolerated dosage Aim to increase perindopril if BP and renal function will allow to the maximum tolerated dosage. Regular bloods for renal function Life Style advice / Education Reduction in salt and advice on changing his diet from convenience foods Reduction in alcohol intake Highlight the importance of compliance of medication Explain possible symptoms and the importance of reporting any changes in symptoms to the HF team. Encourage stopping smoking, referral to cessation, give patches. Discharge Mr Smith is discharged after 4 days on the medical ward, with a plan for FU in the HF clinic in 2 weeks. His U&E s were normal His HR was 70 bpm on 5 mg of Bisoprolol BP 120/80 on perindopril 4 mg His chest was clear Follow up He was seen two weeks later in the HF clinic. His U&Es were checked showing his creatinine had increased to 161 umol/l and urea up to 15.4 umol/l He was reporting symptoms of increasing lethargy and dizziness His HR was 50bpm SR BP 100/50 Treatment plan Reduce Bisoprolol to 2.5 mg Reduced Perindopril back to 2 mg Plan to recheck U&E s in one week Readmitted with worsening HF symptoms Blood renal chemistry deteriorates further despite stopping ACEI – creatinine 288 umol/l Renal review Ongoing management Joint care between HF team and renal team Started on haemodialysis Becomes euvolaemic with improvement in HF symptoms Discussed at HF MDT Further progress Referred for consideration of TAVI in view of severe AS TAVI performed December 2013 Heart Hospital Repeat echo March 2014 shows improvement of LV function to 35% Now on 8mg perindopril, 7.5mg bisoprolol and 25mg spironolactone In NYHA class II EPIDEMIOLOGY AND HEALTH SERVICE IMPACT Size of the problem Summary Common Affects 1-2% of the population Annual incidence is 0.5-1% Serious (but improving) 40% mortality at 1 year, 10% per year thereafter Increasing Ageing population and better treatment of acute MI Disabling Symptoms have enormous impact on quality of life, worse than many other chronic conditions Expensive Around 2% of NHS budget, 5% of acute admissions, and 10% of bed occupancy BMJ, 2002; Eur J Heart Failure, 1999; NICE, 2003; BHF, 2002; DOH 2009 HF GUIDELINES The NICE algorithm for new diagnosis 2010 Adapted from NICE 2010. TREATMENT TREATMENT Aims of treatment of chronic heart failure The aims of therapy in heart failure are to: • Improve life expectancy • Improve quality of life The relative importance of these aims varies: • Between patients • Over time NICE, 2003 TREATMENT Modern management The therapeutic approach in chronic heart failure due to systolic dysfunction consists of: • Non-pharmacological measures Patient education Avoid obesity Dietary measures e.g. salt restriction if prescribed Avoid excessive fluid intake Smoking cessation Exercise/rehabilitation Influenza/pneumococcal vaccination • Pharmacological therapy • Devices and surgery ESC, 2008 TREATMENT Co-morbidities that may impact on treatment (1) Co-morbidity Comments COPD/asthma/reversible Beta-blockers are contraindicated in airways disease patients with reversible airways disease Renal dysfunction (serum creatinine > 200 µmol/l) ACE inhibitors and angiotensin II receptor blockers may be contraindicated Adapted from NICE 2003. NICE, 2003 TREATMENT Treatment options for chronic heart failure Drug therapy Diuretics Neurohormonal antagonists • • • • ACE inhibitors Beta blockers Mineralocorticoid antagonists Angiotensin II receptor blockers Ivabradine (If channel blocker) Digoxin Other drugs • • • • Amiodarone Nitrates/Hydralazine Aspirin Warfarin TREATMENT Diuretic therapy Rapid relief of congestive symptoms and fluid retention, improving: • Breathlessness • Exercise performance May be titrated according to need following initiation of subsequent therapies No evidence for mortality benefit No effect on disease progression “Diuretics should be routinely used for the relief of congestive symptoms and fluid retention in patients with heart failure, and titrated (up and down) according to need following initiation of subsequent heart failure therapies” NICE, 2003 TREATMENT Use of oral diuretics Drug Initial dose (mg) Maximum recommended daily dose (mg) 0.5–1.0 20–40 5–10 5–10 250–500 100–200 Bendroflumethiazide (bendrofluazide) Indapamide Metolazone 2.5 2.5 2.5 5 2.5 10 Potassium-sparing diuretic +ACEI 2.5 25 Loop diuretics Bumetanide Furosemide Torasemide Thiazides* Amiloride Triamterene –ACEI 5 50 +ACEI 20 100 –ACEI 40 200 *May be effective when added to loop diuretics when fluid retention is resistant, but can promote dramatic diuresis and disturbance in fluid balance and electrolytes. Patients must be closely monitored and specialist advice is required. ACEI=ACE inhibitor Adapted from NICE et al. 2003. NICE, 2003 TREATMENT ACE inhibitor therapy for heart failure and LVSD All trials 40 30 Systematic overview of data from five long-term RCTs Compared with placebo, ACE inhibitors reduce: • Mortality (p<0.0001) • Readmission (p<0.0001) • Reinfarction (p<0.0001) Benefit begins early after the start of therapy and persists in the long-term 20 Cumulative mortality (%) 10 0 0 1 2 3 4 5 Time since randomisation (years) ACE-1 Placeb0 6391 6372 5378 5279 4204 4025 2457 2364 892 742 Adapted from Elather et al. 2000. Flather et al, Lancet; 2000 TREATMENT ACE inhibitor therapy for heart failure due to LVSD “All patients with heart failure due to left ventricular systolic dysfunction should be considered for treatment with an ACE inhibitor. ACE inhibitor therapy should be instituted in patients with heart failure due to left ventricular systolic dysfunction before beta-blockade is introduced.” “ACE inhibitor therapy should be initiated at the appropriate dose, and titrated upwards at short intervals (eg every two weeks) until the optimal tolerated or target dose is achieved.” NICE, 2003 TREATMENT Practical recommendations on use of ACE inhibitors (1) How to use Start with a low dose Seek specialist advice where the patient is on a high dose (eg furosemide 80mg) of a loop diuretic Double dose at not less than two weekly intervals Aim for target dose or the highest tolerated dose Remember some ACE inhibitor is better than no ACE inhibitor Monitor blood electrolytes (in particular potassium), urea, creatinine and blood pressure If the patient develops a troublesome dry cough which interferes with sleep and is likely to be caused by an ACE inhibitor, consider substituting an angiotensin-II receptor blocker NICE, 2003 TREATMENT Practical recommendations on use of ACE inhibitors (2) Advice to patients Explain expected benefits Treatment is given to improve symptoms, to prevent worsening of heart failure and to increase survival Symptoms improve within a few weeks to a few months Advise patients to report principal adverse effects, i.e. dizziness/symptomatic hypotension, cough. If the patient develops a troublesome dry cough which interferes with sleep and is likely to be caused by an ACE inhibitor, consider substituting an angiotensin-II receptor blocker NICE, 2003 TREATMENT Beta-blocker therapy for heart failure due to LVSD Bisoprolol pooled (2 trials) Bucindolol pooled (4 trials) Carvedilol pooled (5 trials) Metoprolol pooled (9 trials) 5 small trials Overall (25 trials) 0.1 0.2 0.5 1 2 5 Pooled data from 25 RCTs (6511 patients and 810 deaths) Compared with placebo, beta-blockers reduced odds of death by 36% 10 Fig 1 Pooled odds ratios (and 95% confidence intervals) describing the effect of beta blockers on mortality in patients with heart failure • (95% CI 25% to 45%) ACE inhibitors alone Beta Blockers added No evidence of heterogeneity between trial results Benefit is additional to that of ACE inhibitors Combined effect -8 -6 -4 -2 0 Absolute reduction in mortality in 1 year attributable to treatment (%) Fig 2 Effect on annual rate of mortality (%) of angiotensin inhibitors alone, with beta blockers added, and with both drugs. Risk differences and 95% confidence intervals. Cleland et al, BMJ, 1999 Adapted from Cleland et al. 1999. TREATMENT All patients with heart failure due to LVSD should be considered for treatment with a beta-blocker (2) How to use? Start with a low dose Double dose at not less than two weekly intervals Aim for target dose (see above) or, failing that, the highest tolerated dose Remember some beta-blocker is better than no beta-blocker Monitor heart rate, blood pressure, clinical status (symptoms, signs, especially signs of congestion and body weight) Check blood electrolytes, urea and creatinine one to two weeks after initiation and one to two weeks after final dose titration NICE, 2003 TREATMENT When starting a patient on a beta-blocker (1) Ensure that the patient Understands the expected benefits of beta-blockers: prevent worsening of heart failure improve symptoms (but may take 3-6 months or more) increase survival Knows that symptoms may deteriorate during initiation / uptitration phase Knows that beta-blockers should not be stopped without first seeking advice Understands that any deterioration (tiredness, fatigue, breathlessness) should be reported as this can be easily managed by adjusting other drugs Is encouraged to weigh themselves each day (after waking, before dressing, after voiding, before eating) NICE, 2003 TREATMENT When starting a patient on a beta-blocker (2) If patients experience worsening symptoms/signs Congestion – double dose of diuretic or halve dose of beta-blocker Fatigue – halve dose of beta-blocker (rarely necessary) Review patient in 1-2 weeks; if not improved seek specialist advice Serious deterioration – halve beta-blocker dose or stop treatment and seek specialist advice NICE, 2003 TREATMENT Mineralocorticoid receptor antagonist (MRA) therapy for heart failure due to LVSD Probability of Survival 1.00 The Randomised Aldactone Evaluation Study (RALES) 1663 patients with NYHA III or IV heart failure and ejection fraction ≤35% who were already treated with ACE inhibitor, diuretic ± digoxin Spironolactone 25mg od vs placebo, with patients followed for an average of 2 years 30% reduction in the risk of death (p<0.001) and 35% reduction in risk of hospitalisation (p<0.001) among patients randomised to spironolactone 0.95 0.90 RRR=0.30 (0.18-0.40) 0.85 0.80 0.75 Spironolactone 0.70 0.65 0.60 Placebo 0.55 P < 0.001 0.50 0.45 0.00 0 3 6 9 12 15 18 21 24 27 30 33 36 Months Adapted from Pitt et al. 1999. Pitt et al, N Engl J Med, 1999 TREATMENT NICE recommendation on spironolactone Patients with heart failure due to LV systolic dysfunction who remain moderately to severely symptomatic despite optimal therapy should be prescribed spironolactone at a dose of 12.5 to 50 mg once per day – specialist advice should be sought Patients with heart failure taking spironolactone should have blood potassium and creatinine levels monitored for signs of hyperkalaemia and/or deteriorating renal function. If hyperkalaemia is a problem then the dose of spironolactone should be halved and biochemistry rechecked • Symptom improvement occurs within a few weeks to a few months of starting treatment • Patients should avoid NSAIDs (including OTC products e.g. ibuprofen) • Temporarily stop spironolactone if diarrhoea and/or vomiting and contact physician • Male patients may develop breast discomfort and/or gynaecomastia NICE, 2003 TREATMENT Mineralocorticoid receptor antagonist therapy for heart failure after MI EPHESUS trial Cumulative Incidence (%) 40 3313 patients were randomised to eplerenone 25 mg/day and 3319 to placebo (in addition to ‘standard’ medical therapy). Mean follow-up of 16-months. Among those taking eplerenone there was: p=0.008 RR=0.85 35 30 Placebo 25 • 20 (p=0.008) 15 Eplerenone 10 • 5 0 • 0 3 6 9 12 15 18 21 24 27 30 33 36 Months since Randomization No. at Risk Placebo Eplerenone 15% relative risk reduction in all-cause death 3313 3064 2983 2830 3319 3125 3044 2896 2418 1801 1213 2463 1857 1260 709 728 323 336 99 110 2 0 0 0 0 0 13% relative risk reduction in cardiovascular death or hospitalisation (p=0.002) 21% relative risk reduction in sudden cardiac death ( p=0.03) Compared with spironolactone, eplerenone is less likely to cause gynaecomastia or breast tenderness, but K+ monitoring is still essential. Adapted from Pit et al. 2003. Pitt et al, N Engl J Med, 2003 Primary composite end point (CV death or hospital admission for worsening HF) Cumulative frequency (%) 40 HR = 0.82 (0.75–0.90) Placebo P < 0.0001 18% RRR 30 Ivabradine 20 10 0 0 6 Swedberg K, et al. Lancet. 2010;376:875-885. 12 18 24 30 Months New EU license for ivabradine February 2012 “Ivabradine is indicated in chronic heart failure NYHA II to IV class with systolic dysfunction, in patients in sinus rhythm and whose heart rate is ≥ 75 bpm, in combination with standard therapy including beta-blocker therapy or when beta-blocker therapy is contraindicated or not tolerated.” TREATMENT Digoxin The oldest established treatment for heart failure Digoxin has a narrow therapeutic window Arrhythmias and gastrointestinal side effects are common TREATMENT How useful is digoxin? The DIG trial 6800 patients with heart failure (EF45%) already on diuretic + ACE inhibitor Randomised to digoxin or placebo, 250 g/day (mean dose) and followed for average of 37 months No difference in total mortality (p=0.80) 28% relative risk reduction in death or hospitalisation due to worsening HF (p<0.001) 40 40 Mortality 30 from Any Cause (%) 20 Death or 30 Hospitalisation Due to 20 Worsening Heart 10 Failure (%) 0 Placebo p=0.80 10 Digoxin 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Months Adapted from DIG 1997. Placebo P<0.001 Digoxin 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Months Adapted from DIG 1997. DIG, N Engl J Med, 1997 TREATMENT NICE recommendation on digoxin • Digoxin is recommended for: • worsening or severe heart failure due to LV systolic dysfunction despite ACE inhibitor, beta-blocker and diuretic therapy • patients with atrial fibrillation and any degree of heart failure Several drugs can alter the pharmacokinetics of digoxin, especially: anti-arrhythmic drugs affecting renal clearance and/or volume of distribution (verapamil, amiodarone, propafenone and quinidine) drugs increasing its absorption (erythromycin, omeprazole and tetracycline) drugs decreasing its absorption (colestipol, cholestyramine) NICE, 2003 2012 2012 TREATMENT Other medical treatments (1) Anticoagulants “Anticoagulation is indicated for patients with the combination of heart failure and atrial fibrillation.” “In patients with heart failure in sinus rhythm, anticoagulation should be considered for those with a history of thromboembolism, left ventricular aneurysm, or intracardiac thrombus.” Amiodarone “The decision to prescribe amiodarone should be made in consultation with a specialist. The need to continue the prescription should be reviewed regularly.” “Patients taking amiodarone should have a routine sixmonthly clinical review, including liver and thyroid function tests, including a review of side effects.” NICE, 2003 TREATMENT Other medical treatments (2) Aspirin “Aspirin (75–150 mg once daily) should be prescribed for patients with the combination of heart failure and atherosclerotic arterial disease (including coronary heart disease).” Calcium channel blockers ‘Amlodipine should be considered for the treatment of comorbid hypertension and/or angina in patients with heart failure, but verapamil, diltiazem or short-acting dihydropyridine agents should be avoided” NICE, 2003 TREATMENT Other medical treatments (3) Isosorbide/hydralazine combination “An isosorbide/hydralazine combination may be used in patients with heart failure who are intolerant of ACE inhibitors or angiotensin-II receptor antagonists.” Inotropic agents “Intravenous inotropic agents (such as dobutamine, milrinone or enoximone) should only be considered for the short-term treatment of acute decompensation of chronic heart failure. This will require specialist advice.” NICE, 2003 Statins in chronic heart failure Two randomised controlled trials — CORONA and GISSI-HF — have shown no mortality benefit of statin therapy in patients with chronic heart failure, irrespective of its aetiology Kjekshus et al, N Engl J Med 2007; GISSI-HF investigators, Lancet 2008 ANYTHING NEW? RELAXIN CHRONIC DISEASE MANAGEMENT Patient self-monitoring Patients can monitor their volume status by daily weighing and appropriate adjustment of their diuretic regimen Requires education and support Patients should be taught how to recognise early signs of decompensation and how to seek professional help Heart failure nurse usually most appropriate professional to ‘train’ patient NICE, 2003 CHRONIC DISEASE MANAGEMENT Remote monitoring Typical equipment for telemonitoring Remote monitoring of patients’ clinical status (telemonitoring) can improve access to health care Facilitates earlier detection of deterioration Acceptable and easy to use by patients Likely to become part of a modern heart failure management programme Riley, Heart, 2009 TREATMENT Other treatment options Surgery and devices Cardiac resynchronisation therapy (CRT) Implantable cardioverter defibrillator (ICD) Coronary revascularisation (PCI/CABG) Transplantation Left ventricular assist device (LVAD) Other invasive therapies • Valve repair/replacement • Left ventricular aneurysmectomy NICE, 2003 CHRONIC DISEASE MANAGEMENT Treatment monitoring checklist Follow-up interval should be a maximum of six months NICE, 2010 CHRONIC DISEASE MANAGEMENT Side-effects of drugs commonly used in the treatment of heart failure (2) Digoxin Common: nausea Serious: life threatening arrhythmias Angiotensin II receptor blockers Common: hypotension including postural Serious: worsening renal function, renal infarction in renal artery stenosis Amiodarone Common: photosensitivity, nausea, thyroid dysfunction, sleep disturbance, corneal microdeposits Serious: thyrotoxic storm, pro-arrhythmia, pulmonary/hepatic fibrosis NICE, 2003 CHRONIC DISEASE MANAGEMENT Side-effects of drugs commonly used in the treatment of heart failure (1) Diuretics Common: postural hypotension, gout, urinary urgency Serious: electrolyte imbalance (hypokalaemia, hypomagnesia, hyponatraemia), arrhythmia ACE inhibitors Common: cough, hypotension including postural Serious: worsening renal function, renal infarction in renal artery stenosis, angio-oedema Beta-blockers Common: tiredness, bradycardia, coldness Serious: asthmatic attack, exacerbation of heart failure, heart block Spironolactone Common: gynaecomastia, tiredness, rashes; Serious: hyperkalaemia, hyponatraemia NICE, 2003 CHRONIC DISEASE MANAGEMENT Improving adherence to drug therapy Non-adherence with treatment is associated with a high risk of readmission to hospital Non-adherence may be reduced by: • Simplifying drug dosing regimens • Educating patients/carers about medicines, and the reasons for taking them NICE recommendation: Dosing regimens should be kept as simple as possible, and the healthcare professional should ensure that the patient and carer are fully informed about their medication NICE, 2003 & 2009 CHRONIC DISEASE MANAGEMENT Depression: common and important Consider depression in all patients with heart failure Studies suggest a prevalence of depression of around 30% in non-hospitalised patients with heart failure Diagnosis is more common in those with physical symptoms and poorer physical functioning Depressive symptoms are strongly linked with a worse outcome Rumsfeld et al, 2003; Friedman et al 2001, Jiang et al, 2004 CHRONIC DISEASE MANAGEMENT End of life issues Palliative care aims to improve the quality of life for terminally ill patients and to help family and carers by: • Providing symptom control • Providing psychological and social support • Planning for the future and providing end of life care Specialist palliative care in cancer: • Improves symptom control • Reduces time spent in hospital • Improves patient and carer choice and satisfaction • Reduces overall costs Anecdotal evidence suggests benefit in heart failure Providing palliative care is complex NICE, 2003 CHRONIC DISEASE MANAGEMENT Initiatives in end of life care First National End of Life Care strategy ‘Better Together’ palliative care service for heart failure patients set up by British Heart Foundation and Marie Curie Cancer Care CHRONIC DISEASE MANAGEMENT Communication is essential for good discharge planning Patients with heart failure should generally be discharged from hospital only when their clinical condition is stable and their management plan is optimised The timing of discharge should take into account both patient and carer wishes and the level of care and support that can be provided in the community The primary care team, patient and carer must be aware of the management plan Clear instructions should be given as to how the patient/carer can access advice particularly in the high risk period immediately following discharge NICE, 2003 THANK YOU [email protected]