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Café Cardiologiqué 18th December 2013 Heart Failure Andrew Vanezis PhD Student and Research Fellow Outline • How big a problem is heart failure? • What is heart failure? • Causes • Signs and Symptoms • Investigations • Current Therapies for Chronic HF • Up-coming therapies / Research areas How big a problem is it? • ~ 900,000 people in the UK have heart failure • Similar number have heart damage but no symptoms • Average age of first diagnosis = 76 with incidence and prevalence increasing with age • 30–40% of patients diagnosed with heart failure die within a year but thereafter the mortality is < than 10% per year BHF, Leicestershire County Council, Experian, SEPHO How big a problem is it? • Costs the NHS ~ £1.2 billion per year, ~75 % of which is due to repeated hospitalisations • Some hope…6-month mortality rate ↓ from 26% in 1995 to 14% in 2005 • In 2010/11 the emergency admission rate for heart failure in the East Midlands was 63.2 per 100,000, significantly ↑ than England overall (59.8 per 100,000) BHF, Leicestershire County Council, Experian, SEPHO What is heart failure? • Nebulous term that describes a syndrome, not a specific diagnosis • Broadly speaking: When the heart can not meet the metabolic demands of the body, usually (but not exclusively) due to a ↓ cardiac output Some physiology… Some physiology… Cardiac Output = Heart Rate x Stroke Volume Some physiology… Cardiac Output = Heart Rate x Stroke Volume End Diastolic Volume – End Systolic Volume Some physiology… Cardiac Output = Heart Rate x Stroke Volume End Diastolic Volume – End Systolic Volume Preload Myocardial contractility Afterload Spiral into oblivion… • Spiral phenomenon: Defining heart failure? Defining heart failure? • Systolic and Diastolic Defining heart failure? • Systolic and Diastolic • HF-PEF and HF-REF Defining heart failure? • Systolic and Diastolic • HF-PEF and HF-REF • Left and Right Defining heart failure? • Systolic and Diastolic • HF-PEF and HF-REF • Left and Right • Congested and Cor Pulmonale Defining heart failure? • Systolic and Diastolic • HF-PEF and HF-REF • Left and Right • Congested and Cor Pulmonale • High output and Low output Defining heart failure? • Systolic and Diastolic • HF-PEF and HF-REF • Left and Right • Congested and Cor Pulmonale • High output and Low output • Acute and Chronic Defining heart failure? • Systolic and Diastolic • HF-PEF and HF-REF • Left and Right • Congested and Cor Pulmonale • High output and Low output • Acute and Chronic • Forward and Backward Defining heart failure? • Systolic and Diastolic • HF-PEF and HF-REF • Left and Right • Congested and Cor Pulmonale • High output and Low output • Acute and Chronic • Forward and Backward Symptoms LEFT • Decreased exercise tolerance • Cough • Short of breath lying flat • Awaking gasping for air BOTH RIGHT • Shortness of • Oedema (of the Breath extremities, scrotum, • Fatigue • Changes in weight abdomen) • Abdominal pain Signs LEFT • Crackles or wheezes in chests • Frothy/blood stained sputum • Confusion • Blue extremities BOTH • Fast heart rate/ irregular rhythm • Fast breathing rate • Valve Murmurs related to increase volume and pressure RIGHT • Oedema (leg/sacral etc.) • Elevated neck vein pressure • Enlarged liver • Chronic venous leg changes • Fluid at lung bases • Free fluid in the abdomen • ?Primary lung cause Stratifying severity • NYHA class: I. No symptoms with ordinary activity II. Mild symptoms (e.g. shortness of breath) and slight limitation during ordinary activity III. Marked limitation in activity due to symptoms, even during less-than-ordinary activity. Comfortable only at rest. IV. Usually bed-bound as has severe limitations. Experiences symptoms even at rest. Stratifying severity • NYHA class: I. No symptoms with ordinary activity II. Mild symptoms (e.g. shortness of breath) and slight limitation during ordinary activity III. Marked limitation in activity due to symptoms, even during less-than-ordinary activity. Comfortable only at rest. IV. Usually bed-bound as has severe limitations. Experiences symptoms even at rest. • Detailed lifestyle questionnaires • Objective exercise assessment e.g. 6 min walk test / bleep test – especially VO2 max Aetiology • • • • • • • • • • Ischaemic Heart Disease (50%) Hypertension Diabetes Aortic stenosis Congenital Alcohol Viral e.g. peri/myocarditis Infiltrative e.g. amyloidosis/sarcoidosis HIV Non-cardiac illnesses that could affect the heart indirectly: • • • • Hyperthyroidism Anaemia Paget’s disease Pregnancy Diagnosis of Heart Failure • Good clinical history and examination • Chest X-ray • ECG • BNP/NT-ProBNP • Echocardiogram • Cardiac MRI • Anything that elucidates aetiology! • Other investigations if alternative diagnosis suspected BNP • Peptide released by ventricles due to excessive stretching • NT-proBNP inactive peptide released along with BNP but remains in body twice as long • False + in.. • Chronic obstructive pulmonary disease, hypertrophy of the heart, sepsis, renal failure and old age • False – in.. • Obesity and use of heart failure meds Echo • • • • Transthoracic in first instance Doppler flow is very useful Mainly looking at LV size, mass and function Ejection fraction can be assessed visually, commonly with Simpson’s bi-planar technique which good accuracy • Other structural/valvular abnormalities Management aims • Reduce signs and symptoms (mainly of congestion) – Morbidity • Prolong life – Mortality • Some therapies target morbidity or mortality • Some have benefits to both Management • Identify and treat underlying cause • Lifestyle changes • • • • • • Smoking cessation Reduced salt intake Reduced alcohol intake Exercise Weight loss Education • Psychological • Immunisations • Links to appropriate services e.g. cardiac rehab, heart failure nurses, social workers etc. • Drug therapy • Devices • Palliative and supportive care Management • Identify and treat underlying cause • Lifestyle changes • • • • • • Smoking cessation Reduced salt intake Reduced alcohol intake Exercise Weight loss Education • Psychological • Immunisations • Links to appropriate services e.g. cardiac rehab, heart failure nurses, social workers etc. • Drug therapy • Devices • Palliative and supportive care Ace Inhibitors • Ramipril, Enalapril, Lisinopril, Captopril, Perindopril Ace Inhibitors • Ramipril, Enalapril, Lisinopril, Captopril, Perindopril ACEi Ace Inhibitors • Mortality and Morbidity benefits • Used in all stages of HF • Given irrespective if high BP or not • ↓ Angiotensin 2 effects = • ↓ sympathetic activity and ↑ parasympathetic activity • ↓ salt and water retention (via ↓ aldosterone, ADH and direct effects) • ↓ arterial vasoconstriction and hence ↓BP • Other (proto-oncogenes, fibrosis, apoptosis) • CONSENSUS and SOLVD trials • • The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med. 1987. 316 (23): 1429–35. 35.Jump up The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991 325 (5): 293–302. Angiotensin Receptor 2 Blockers • Losartan, irbesartan, candesartan • Mortality and Morbidity benefits • Used in all stages of HF • No added benefit with ACEi in combination • Usually used if ACEi not tolerated • Can be used first line in: • HF post heart attack • Chronic HF and systolic dysfunction Beta-blockers • Bisoprolol, metoprolol, carvedilol, atenolol • Morbidity and mortality benefit • Improved survival in NYHA class II to III HF ± probably class IV Beta-blockers • Slow heart rate (B1 blocking effect) therefore better pumping mechanics • For every 5bpm ↓, relative risk of death ↓ by 18% (McAlister FA, et al. Ann Int Med 2009;150:784) • ↓ Renin secretion = reduced sodium and water retention • ↓ Angiotensin 2 production • Other unknown affects on LV remodelling • CIBISII and MERIT-HF trials • • CIBIS II investigators and Committees. The Cardiac Insufficiency Bisoprolol Study II (CIBIS II): a randomized trial. Lancet. 1999;353:9–13. MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in-Congestive Heart Failure (MERIT-HF). The Lancet. 1999. 353, 9169, 2001 - 2007 Loop Diuretics • Furosemide, Bumetanide • Morbidity benefits only • Used in moderate and severe HF • Powerful diuretics acting at loop of Henle Na+/K+/2Clcotransporters competing with CL- binding site • Can be supplemented with other classes of diuretics e.g. thiazide/thiazide like to improve diuresis • Long term use can lead to renal dysfunction, worsening heart failure • ADHERE registry • Peacock WF et al. Impact of intravenous loop diuretics on outcomes of patients hospitalized with acute decompensated heart failure: insights from the ADHERE registry. Cardiology. 2009;113(1):12-9. Aldosterone antagonists • Spironolactone, epleronone • Morbidity and mortality benefit • Potassium sparing diuretic (weak) • Acts at collecting tubules – competitive inhibitor of aldosterone which works via Na+/K+ pumps • Used in NYHA class III and IV • Especially useful in MI induced HF • Augments effect of ACEi and loop diuretics • RALES and EPHESUS trials • • Pitt B et al . The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure. N Engl J Med. 1999. 341 (10): 709–717. Pitt B et al . The EPHESUS trial: eplerenone in patients with heart failure due to systolic dysfunction complicating acute myocardial infarction. Eplerenone Post-AMI Heart Failure Efficacy and Survival Study. Cardiovasc Drugs Ther. 2001. 15 (1): 79–87. Ivabradine • Morbidity and Mortality benefits (but only one trial) • Acts on funny channel (mixed inward Na+/K+) in sinus node reducing the steepness of diastolic depolarization curve • Main effects from heart rate lowering therefore used if HR still >75 despite maximal beta blocker use • Use in II-IV stable chronic HF with systolic dysfunction • SHIFT trial • Swedberg, K et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet 2010. 376, 9744, 875 - 885 Hydralazine and nitrates • Mortality and Morbidity benefits • NYHA II-IV HF • Hydralazine = arterial vasodilator = ↓afterload • Nitrate = venous vasodilators = ↓preload • African/Caribbean origin • May have role in Diastolic heart failure Digoxin • Morbidity benefits only • Blocks Na+/K+ ATPase pump in myocytes – eventual effect = ↑ intracellular calcium = lengthening of phase 4 and 0 of action potential and ↓ heart rate • Slight ↑ pumping and slight ↓ heart rate • Often used if concurrent atrial fibrillation • Lots of side effects Drugs – other issues • Drugs often prescribed at sub-optimal doses • Poor concordance with many cardiac drugs • Most research in relation to Left Ventricular Systolic Dysfunction therefore treatment in other forms is often extrapolation Cardiac Resynchronisation Therapy Left Ventricular Assist Devices Cardiac Transplant Christiaan Barnard 1967 ESC guidelines 2012 algorithm Palliative care Research Avenues • New drugs • Renin blockers • Serelaxin • Ularitide • Stem cells • Heart (multi-potent cardiac progenitor cells) • Bone marrow mobilisation • Re-programming non mycoytes Research Avenues • Gene Therapy • SERCA2a trials Imperial College/Brompton – ongoing in naive HF and LVAD patient • MicroRNA • Early days • Much focus on muscle-specific microRNAs within MHC genes (control myosin expression + response of the heart to stress) • Remote Ischaemic Conditioning • DREAM and CRIC trials Thanks and Merry Christmas!