Chronic Heart Failure. Dr Eric Klug Heart Failure Clinic: CM Johannesburg Academic Hospital. Sunninghill and Sunward Park Hospitals

Transcription

1 Chronic Heart Failure Dr Eric Klug Heart Failure Clinic: CM Johannesburg Academic Hospital. Sunninghill and Sunward Park Hospitals

2 The most important slide: The challenge of chronic The good physician knows his patients through and through, and his knowledge is bought dearly. Time, sympathy, and understanding must be lavishly dispensed, but the reward is to be found in that personal bond which forms the greatest satisfaction of the practice of medicine. One of the essential qualities of the clinician is interest in humanity, for the secret of the care of the patient is in caring for the patient Francis W Peabody 1927

3 Diagnosis ( HEART FAILURE IS A SYNDROME) Establish the cause: Pericardial; Epicardial; Myocardial; Endocardium; Electrical; Valvular Tight Aortic Stenosis (valve area below.8cm squared) can be a challenging diagnosis in heart failure Often high risk individuals Consider TAVI

4 Does heart failure kill? Long term survival of cancer patients compared to heart failure and stroke: A systematic review (2003 9) Among diseases responsible for the majority of deaths worldwide, cancer, heart failure and stroke possess leading positions 5 year survival after diagnosis was about 43% for all cancer diseases 5 year survival for heart failure varied between 26% and 52% 5 year survival after a stroke event varied between 40% and 68% BMC Cancer. 2010; 10: 105

5 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure Released 21 May 2016 HFpEF HFrEF HFmrEF Randomised HF REF trials have used an entry LVEF <35%. Most of the medications indicated in HF REF, have been studied in trials where the EF was <35%. The definition of HF REF, however, is an EF <50%. To avoid confusion between the inclusivity of the definition and the exclusivity of the randomised trials, we have taken a different approach to that of the ESC guideline S Afr Med J 2013;103(9 Suppl 2): DOI: /SAMJ.7319

6 What is this HF PEF? Outcomes in Patients With HF-PEF Versus Those in Hypertension Trials Outcomes in Patients With HF-PEF Versus HF-REF (J Am Coll Cardiol 2012;60: )

7 LV Remodeling The vicious cycle of heart failure Cardiac injury (e.g. MI) Infarct zone Spherical ventricular thinning and elongation dilation Ventricle Increased Interstitial collagen Fibrous scar Myocyte hypertrophy Konstam et al. J Am Coll Cardiol 2011;4: Mohammad Sarraf et al. CJASN 2009;4:

8 BNP Rule out level BELOW 125 pg/ml excludes cardiac dysfunction (300pg/ml in AHF) Rule in level (still to be established) 450 pg/ml : < 50 yrs 900 pg/ml : yrs 1800 pg/ml : > 75 yrs 4200 pg/ml : > 86 years

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10 HF-REF: The Building Blocks The pyramid of therapy Diuretic of Therapy European Journal of Heart Failure Volume 17, Issue 3, pages , 9 MAR 2015 DOI: /ejhf.250 ARNI

11 Evolution of pharmacologic approaches in HF: Neprilysin inhibition as a new therapeutic strategy SNS β blockers NP system Neprilysin inhibitors HF SYMPTOMS & PROGRESSION Epinephrine Norepinephrine α 1, β 1, β 2 receptors Vasoconstriction RAAS activity Vasopressin Heart rate Contractility NPRs NPs Vasodilation Blood pressure Sympathetic tone Natriuresis/diuresis Vasopressin Aldosterone Fibrosis Hypertrophy INACTIVE FRAGMENTS RAAS Ang II AT 1 R Vasoconstriction Blood pressure Sympathetic tone Aldosterone Hypertrophy Fibrosis RAAS inhibitors (ACEI, ARB, MRA) Neprilysin inhibitors: natriuretic and other vasoactive peptides enhancement 11 ACEI=angiotensin converting enzyme inhibitor; Ang=angiotensin; ARB=angiotensin receptor blocker; AT 1 R= angiotensin II type 1 receptor; HF=heart failure; MRA=mineralocorticoid receptor antagonist; NP=natriuretic peptide; NPRs=natriuretic peptide receptors; RAAS=reninangiotensin aldosterone system; SNS=sympathetic nervous system 1. McMurray et al. Eur J Heart Fail 2013;15: Figure references: Levin et al. N Engl J Med 1998;339:321 8; Nathisuwan & Talbert. Pharmacotherapy 2002;22:27 42; Kemp & Conte. Cardiovascular Pathology 2012;365 71; Schrier & Abraham N Engl J Med 2009;341:577 85

12 Neprilysin inhibition must be accompanied by simultaneous RAAS blockade Neprilysin metabolizes Ang I and Ang II via several pathways Inhibition of neprilysin alone is insufficient as it associated with an increase in Ang II levels, counteracting the potential benefits of neprilysin inhibition Neprilysin inhibition must be accompanied by simultaneous RAAS blockade (e.g. AT 1 receptor blockade) Angiotensinogen Ang I Ang II Renin ACE Neprilysin inhibitor AT 1 receptor Neprilysin Neprilysin inhibitor Neprilysin Ang (1 7) Inactive fragments Signaling cascade Biological actions Hypertrophy Fibrosis Vasoconstriction Hypertrophy Na + /H 2 O retention Aldosterone release Norepinephrine release Sympathe c tone 12 ACE=angiotensin converting enzyme; AT 1 =angiotensin II type 1; Ang=angiotensin; H 2 0=water; Na=sodium; RAAS=renin angiotensin aldosterone system 1. Von Lueder et al. Circ Heart Fail 2013;6: Langenickel & Dole. Drug Discov Today: Ther Strateg 2012;9:e131 9

13 PARADIGM HF: the largest mortality morbidity PARADIGM HF trial in MENU patients with HFrEF 10,000 9,000 N=8442 8,000 Number of patients 7,000 6,000 5,000 4,000 3,000 2,000 1,000 N=2569 N=2548 N=3834 N=1798 N=6505 N= SOLVD T CHARM Added HEAAL RAFT SHIFT EMPHASIS HF PARADIGM HF Recruitment CHARM Added=Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity Added trial; EMPHASIS HF=Eplerenone in Mild Patients Hospitalization And Survival study in Heart Failure; HEAAL=Heart failure Endpoint evaluation of Angiotensin II Antagonist Losartan; HFrEF=heart failure with reduced ejection fraction; PARADIGM HF=Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure; RAFT=Resynchronization/Defibrillation for Ambulatory Heart Failure Trial; SHIFT=Systolic Heart Failure Treatment with the I f Inhibitor Ivabradine Trial; SOLVD T=Studies of Left Ventricular Dysfunction Treatment trial McMurray et al. Eur J Heart Fail 2014;16:817 25

14 PARADIGM HF MENU PARADIGM HF: To evaluate the effect of LCZ mg BID compared with enalapril 10 mg BID, in addition to conventional HFrEF treatment, in delaying time to first occurrence of either CV death or HF hospitalization,ef <35 40%, NT probnp > 600pg/ml. Randomization n=8442 Double blind Treatment period Single blind active run in period LCZ mg BID Enalapril 10 mg BID* LCZ mg BID LCZ mg BID Enalapril 10 mg BID # 2 Weeks 1 2 Weeks 2 4 Weeks. Median of 27 months follow up On top of standard HFrEF therapy (excluding ACEIs and ARBs) 14 *Enalapril 5 mg BID (10 mg TDD) for 1 2 weeks followed by enalapril 10 mg BID (20 mg TDD) as an optional starting run in dose for those patients who are treated with ARBs or with a low dose of ACEI; 200 mg TDD; 400 mg TDD; # 20 mg TDD. ACEI=angiotensin converting enzyme inhibitor; ARB=angiotensin receptor blocker; BID=twice daily; HFrEF=heart failure with reduced ejection fraction; PARADIGM HF=Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure; TDD=total daily dose McMurray et al. Eur J Heart Fail 2013;15: McMurray et al. Eur J Heart Fail 2014;16: McMurray et al. N Engl J Med 2014;371:

15 Key clinical outcomes in PARADIGM HF European Journal of Heart Failure Volume 17, Issue 3, pages , 9 MAR 2015 DOI: /ejhf fig 0003

16 ESC Guideline 2016 CLASS 1, LEVEL B recommendation to replace an ACE I to further reduce the risk of HF hospitalisation and death in ambulatory patients in HFrEF patients who remain symptomatic despite optimal treatment with an ACE I, a betablocker and a MRA Doi: /eurheartj/ehw128

17 ECG

18 Primary Prevention Timing of device therapy in symptomatic HF The ESC guideline indicates that in primary prevention, an ICD is recommended in a patient with symptomatic HF ( NYHA FC II III ) and an EF < 35% despite at least 3 MONTHS of treatment with optimal pharmacological therapy who are expected to survive more than 1 year CRT is considered in a symptomatic patient on OMT, with QRS > 130ms, EF<35%, and preferably LBBB. (SR or AF). Strong recommendation if QRS > 150 ms.

19 CRT P/ CRT D

20 18 SECONDS PRIOR TO CARDIOVERSION FROM VF OCT 2012 (Initial presentation June 2012)

21 Episode of VFLUTTER cardioverted by the ICD in March 2015

22 Finally Chronic heart failure therapy involves commitment from the doctor, patient and health funder Attention to detail is fundamental Although initial rest, removal from work is necessary sometimes for months, the ultimate aim is to return the patient to normal working life, travel and recreation An exercise program once stable is encouraged to re condition Following guideline mandated therapy in chronic heart failure is a minimum requirement! DEFIBRILLATORS in heart failure save lives!!

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25 Liraglutide ( GLP 1 agonist increases heart rate in heart failure patients DDP IV inhibitors cause more heart failure We currently don't know how to treat diabetes in heart failure

26 Outcomes in Patients With HF-PEF Versus Those in Other Cardiovascular Trials 2 things that most clearly differentiate patients with HF-PEF from those with hypertension is having the clinical syndrome of heart failure (and often previous hospital admission with heart failure) and elevated natriuretic peptide levels (J Am Coll Cardiol 2012;60: )

27 ESC Guideline: European Heart Journal (2012) 33,

28 BNP The heart is an endocrine organ Guideline: Class I recommendation BNP or NT probnp values in the diagnosis of heart failure in ambulatory patients with dyspnea, especially when the diagnosis is uncertain The clinical impression of heart failure must be confirmed by objective tests,establishing diagnosis, aetiology and precipitating factor/s

29 1 mg/dl 88.4 µmol/l 2 mg/dl µmol/l

30 Atrial Fibrillation Population, Stroke Risk and the Left Atrial Appendage AFib increases risk of stroke 5x greater risk of stroke with AFib 1 35% of AF patients will have a stroke in their lifetime Blood clots form in the left atrial appendage 10% 90% Thrombus Originate LAA Many patients are unprotected Non LAA 15% 10% 30 40% 70% of patients are unwilling or unable to take Warfarin UNDERUTILISATION COMPLIANCE BLEEDINGThrombus Originate LAA EXPENSE UNWILLING STROKES IN USA ANNUALLY AF ASSOCIATED WITH APPROX 25% Stroke is more severe for patients with AF 3RD LEADING CAUSE OF DEATH IN USA 1 Holmes DR. Seminars in Neurology. 2010;30: Blackshear JL. Odell JA., Annals of Thoracic Surgery. 1996;61:

31 South Africa SA patients (98) entered into ACTIVE W trial Mean TTR 46.3% (63.4% world wide) SA worst performing country in the study SA patients (98) entered into ACTIVE W trial Mean TTR 46.3% (63.4% WORLD WIDE CVJA 2011;22:220

32 LAA source of clot (>90%) Fibrillation causes blood to stagnate in the LAA The stagnant blood becomes an ideal environment for a thrombus or blood clot to form The blood clot, or portion of it, dislodges from the LAA and travels through arterial system

33 The challenge of diuretics

34 Sustained over activation of the RAAS Cardiac dysfunction leads to RAAS activation sustained over activation puts further strain on the weakened heart, creating a vicious cycle RAAS suppression as an effective strategy in treating HF Hypertrophy Fibrosis Cardiac remodeling Myocyte necrosis Sympathe c tone Heart rate Contrac lity ACE Sodium and water retention Blood volume ACEIs ARBs MRAs Angiotensinogen Direct renin inhibitors* Ang I Ang II Adrenal gland Aldosterone Renin Vasoconstriction Hypertrophy Blood pressure Vasopressin Pituitary gland Water absorption Blood volume *Studies ongoing; not approved for treatment of HF 34 ACE=angiotensin converting enzyme; ACEI=angiotensin converting enzyme inhibitor; ARB=angiotensin receptor blocker; Ang=angiotensin; HF=heart failure; MRA=mineralocorticoid receptor antagonist; RAAS=renin angiotensin aldosterone system Zaman et al. Nat Rev Drug Discov 2002;1: Schrier, Abraham. N Engl J Med 1999;341:577 85; Brewster et al. Am J Med Sci 2003;326:15 24; Schmeider. Am J Hypertens 2005;18: ; McMurray et al. Eur Heart J 2012;33:

35 Natriuretic peptides: source, functions, degradation NPR A Cardiomyocytes 1 ANP and BNP NPR B Endothelial cells 1 CNP NPR C ANP BNP CNP NEP Neprilysin Inactive cleavage products GTP cgmp Vasodilation 1,2 Antihypertrophy 1,2 Antiproliferation 2 Vascular regeneration 1 Myocardial relaxation 1 Diuresis, natriuresis 1,2 Antiapoptosis 1 Anti aldosterone 1 Renin secretion inhibition 1,3 Reduced sympathetic tone 4 Lipolysis 1 GTP cgmp Vasodilation 1,2 Antihypertrophy 1,2 Antiproliferation 2 Vascular regeneration 1 Venodilation 1 Antifibrosis 1 Endocytosis Inactivation of NPs 1,2,5 Receptor recycling NP degradation and clearance NP signaling and effects 35 ANP=atrial natriuretic peptide; BNP=B type natriuretic peptide; cgmp=cyclic guanosine monophosphate; CNP=C type natriuretic peptide; GTP=guanosine triphosphate; NP=natriuretic peptide; NPR=natriuretic peptide receptor 1. Mangiafico et al. Eur Heart J 2013;34:886 93; 2. Gardner et al. Hypertension 2007;49:419 26; 3. Pandey. J Am Soc Hypertens 2008;2:210 26; 4. Levin et al. N Engl J Med 1998;339; Von Lueder et al. Pharmacol Ther ;144:41 9

36 NNT to reduce mortality

37 Main challenges: poor short-term and long-term survival Death rate (%) year 3 years 5 years 10 years 20 0 Hillingdon 1,2 (UK) NICOR 2 (UK) Rochester 3 (USA) Worcester 4 (USA) Scotland 5 (UK) Scotland 6 (UK) 1. Cowie MR et al. Heart. 2000;83: Cleland J et al. London: National Institute for Cardiovascular Outcomes Research, Roger VL et al. JAMA. 2004;292: ; 4. Joffe SW et al. J Am Heart Assoc. 2013;2:e000053; 5. Jhund PS et al. Circulation.2009;119: MacIntyre K et al. Circulation 2000;102:1126.

38 The challenge of chronic The good physician knows his patients through and through, and his knowledge is bought dearly. Time, sympathy, and understanding must be lavishly dispensed, but the reward is to be found in that personal bond which forms the greatest satisfaction of the practice of medicine. One of the essential qualities of the clinician is interest in humanity, for the secret of the care of the patient is in caring for the patient Francis W Peabody

39 Outcomes in Patients With HF-PEF Versus HF-REF (J Am Coll Cardiol 2012;60: )

40 Remodeling in patients with HFrEF Cardiac injury (e.g. MI) Infarct zone thinning and elongation Spherical ventricular dilation Ventricle Increased Interstitial collagen Fibrous scar Myocyte hypertrophy 40 HFrEF=heart failure with reduced ejection fraction; MI=myocardial infarction Konstam et al. J Am Coll Cardiol 2011;4:98 108

41 Activation of three major neurohormonal systems Sympathetic nervous system Natriuretic peptide system NPRs NPs Vasodilation Blood pressure Sympathetic tone Natriuresis/diuresis Vasopressin Aldosterone Fibrosis Hypertrophy HF SYMPTOMS & PROGRESSION Epinephrine Norepinephrine Renin-angiotensinaldosterone system Ang II α 1, β 1, β 2 receptors Vasoconstriction RAAS activity Vasopressin Heart rate Contractility AT 1 R Vasoconstriction Blood pressure Sympathetic tone Aldosterone Hypertrophy Fibrosis 41 Ang=angiotensin; AT 1 R=angiotensin II type 1 receptor; HF=heart failure; NPs=natriuretic peptides; NPRs=natriuretic peptide receptors; RAAS=renin angiotensin aldosterone system Levin et al. N Engl J Med 1998;339:321 8 Nathisuwan & Talbert. Pharmacotherapy 2002;22:27 42 Kemp & Conte. Cardiovascular Pathology 2012; Schrier & Abraham. N Engl J Med 2009;341:577 85

42 Categories of AHF end result of a relatively slow (days to weeks) deterioration of severe chronic HF rapidly progressive disorder of high blood pressure (BP) accompanied by severe acute dyspnea Am Heart J 2008;155:9-18

43 Forrester Haemodynamic subsets

44 The challenge of rhythm Atrial Fibrillation Increased risk of TE Impair cardiac function Anticoagulation Rhythm Control Cardioversion Pharmacology Electrophysiology Rate Control Pharmacology Electrophysiology

45 The challenge of rhythm Atrial Fibrillation Anticoagulation assess risk CHA2DS2 VASc >2 recommended DOACS Warfarin HAS BLED <3 recommended Increased risk of TE

46 Atrial Fibrillation,Stroke Risk and the Left Atrial Appendage Many patients are unprotected Blood clots form in the left atrial appendage 30 40% of patients are unwilling or unable to take Warfarin UNDERUTILISATION COMPLIANCE BLEEDING EXPENSE UNWILLING Non LAA 10% 90% Thrombus Originate LAA 10% 15% 70% Thrombus Originate LAA 1 Holmes DR. Seminars in Neurology. 2010;30: Blackshear JL. Odell JA., Annals of Thoracic Surgery. 1996;61:

47 LAA Anatomy OUR MOST LETHAL HUMAN ATTACHMENT Pectinate Muscles Veinot J et al. Circulation 1997;96: Eur J Cardiothorac Surg 2000;17:718

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49 Watchman TM Constrained Device Distal Marker Band Bernhard Meier et al. Europace 2014;16:

50 J Am Coll Cardiol Intv 2010;3:870 7

51 LCZ696 is a first in class angiotensin receptor neprilysin inhibitor (ARNI) LCZ696 is a novel drug which delivers simultaneous neprilysin inhibition and AT 1 receptor blockade LCZ696 is a salt complex that comprises the two active components: sacubitril (AHU377) a pro drug; further metabolized to the neprilysin inhibitor LBQ657, and valsartan an AT 1 receptor blocker in a 1:1 molar ratio 3D LCZ696 structure Bloch & Basile. J Clin Hypertens 2010;12: Gu et al. J Clin Pharmacol 2010;50: Langenickel & Dole. Drug Discov Today: Ther Strateg 2012;9:e131 9

52 PARADIGM HF: summary of baseline PARADIGM HF characteristics MENU Characteristic* LCZ696 Enalapril (n=4,187) (n=4,212) Age, years 63.8 ± ± 11.3 Women, n (%) 879 (21.0) 953 (22.6) Ischemic cardiomyopathy, n (%) 2,506 (59.9) 2,530 (60.1) LV ejection fraction, % 29.6 ± ± 6.3 NYHA functional class, n (%) II III 2,998 (71.6) 969 (23.1) 2,921 (69.3) 1,049 (24.9) SBP, mmhg 122 ± ± 15 Heart rate, beats/min 72 ± ± 12 NT probnp, pg/ml (IQR) 1,631 (885 3,154) 1,594 (886 3,305) BNP, pg/ml (IQR) 255 ( ) 251 ( ) History of diabetes, n (%) 1,451 (34.7) 1,456 (34.6) Treatments at randomization, n (%) Diuretics 3,363 (80.3) 3,375 (80.1) Digitalis 1,223 (29.2) 1,316 (31.2) β blockers 3,899 (93.1) 3,912 (92.9) Mineralocorticoid antagonists 2,271 (54.2) 2,400 (57.0) ICD 623 (14.9) 620 (14.7) CRT 292 (7.0) 282 (6.7) 52 *Mean ± standard deviation, unless stated. BNP=B type natriuretic peptide; CRT=cardiac resynchronization therapy; ICD=implantable cardioverter defibrillator; IQR=interquartile range; LV=left ventricular; NT probnp=n terminal pro B type natriuretic peptide; NYHA=New York Heart Association; PARADIGM HF=Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure; SBP=systolic blood pressure McMurray et al. N Engl J Med 2014;371:

53 Mrs V.M. presents in June years old Diabetic for 9 years, on metformin 500 mg daily Hypertensive for 5 years on Telmisartan 80 mg daily Hypothyroid on 200 ug thyroxine Brother died aged 43 from MI, father at 60 from MI Non smoker Total cholesterol 5, HDL 1.2 and LDL 3.7 mmol/l Presents in heart failure with no history of chest pain

54 Mrs V.M. clinical, ECG, blood tests, echo BP 107/90; Pulse rate 100 beats per min and regular; tachypnoeic on undressing, JVP raised 6cm, bilateral pedal oedema, cool peripheries LV apex displaced and myopathic, S3 left sided gallop, 2/6 MRSM Dull R base of lung, diminished vocal resonance CXR CTR 60%, ULBD, R pleural effusion ECG next slide Echo dilated LV (76 mm), EF 16%, LA 58mm, E/A 2.33, DT 80 ms, E/E 17, IVC 32 mm and non collapsing, PAP 55 mmhg, mild mitral regurgitation, dyskinetic anterior LV wall, with a contracting infero posterior wall Creat 59, Na 134, GGT 62, TB 22, hstt 19, HbA1C 10.5%, TSH 0.17

55 Introduction of prognostic drugs The big 3 Usually within hrs after admission and diuresis ACEI, MRA and beta blocker can be started in low doses and gradually up titrated All 3 are often started simultaneously, encourages compliance on discharge An approach is to use 25 mg spironolactone/eplerenone, start low dose ACEI enalapril 2.5 mg bd ( ramipril 1.25 mg bd; lisinopril 2.5 mg daily) and carvedilol mg bd or bisoprolol 1.25 mg daily and often up titrate the beta blocker before maximising the ACEI dosenot all on same admission but with close OPD follow up The diuretic dose can and should be reduced as up titration of the big 3 continue, with fluid restriction

56 Coronary angiography and chronic heart failure The first priority is to treat the symptoms of the patient and start and uptitrate the big 3 If resting ischaemia/acs is diagnosed, urgent coronary angiography is advised If the patient is symptomatic of angina then early (on the first admission) coronary angiography is advised In a stable patient, responding to standard heart failure care, but the CAD suspicion remains, then elective coronary angiography is suggested with or without viability testing CT coronary angiography may be a good first alternative to screen for CAD and allow planning of subsequent revascularisation options

57 Coronary angiogram Tight LAD 2 lesions including proximally Tight Circumflex proximally and tight ramus intermedius Normal RCA filling the LAD retrograde LVEDP = 32 mmhg LV ejection fraction 22% No viability study as medical aid unsupportive Stenting of all 4 stenoses with DES, uncomplicated

58 3 months later September : CRT D The LV lead proved technically impossible due to anatomic reasons Paced RV and RA but paced in VVI back up mode at 50 beats/minute so as not to pace unless significantly bradycardic and ICD programmed for VF only and VT to be monitored Presented October with VF and survived a successful Shock with 34J, duration 18 secs Her family doctor had placed her on cipramil 20 mg, QTC was 602 ms. Cipramil stopped Carvedilol uptitrated to 25 mg bd by November and heart rate 69/minute After resigning initially, returns to full time employment in June 2013 a year after first presenting ProBNP in January 2014 is 295pg/ml on enalapril 10 mg bd, cardvedilol 25 mg bd, spironolactone 25 mg daily, Lasix 40 mg daily and atorvastatin 40 mg daily, aspirin 100 mg daily EF unchanged from initial admission! Had further ventricular arrhythmias and treated VF episode January 2015 with 35J shock duration of episode 17 seconds

59 ECG November 2012 heart rate 66 b/min

60 Lessons from this case Diabetics, women are more likely to present atypically with CAD often silent ischaemia A steady, thorough approach to all aspects of diagnosis, aetiology and precipitating factors is successful Coronary angiography once stable Stopping toxic anti depressants ( be aware of QT prolonging drugs) Having normal renal function favours a better heart failure prognosis Gradually, persistently maximising the big 3 is crucial, adding other agents according to guideline mandated therapy must be followed Being aware of the crucial role of device therapy (CRT P/D) and timely insertion. Individualise and assess patient context if more invasive options to be considered (like epicardial leads) Understanding that a persistently low EF does not prevent the patient from improving clinically EF does not relate to functional class