Contemporary heart failure management. Dr Joris Mekel GP meeting 26 March 2015

Transcription

1 Contemporary heart failure management Dr Joris Mekel GP meeting 26 March 2015

2 Case 1 Mr T. McI. 49 years Viral illness June 2014 Progressive dyspnoea to NYHA FC III 6-8 mid-strength beers/day Unremarkable blood tests

3 Case 1 PID: /22/ :25:00 MCINNERNEY, TROY 05/20/1965 DOB 49 years Male Dept Rx: Dx: Rate 104 PR 182 QRSD 108 QT 342 QTc AXIS-- P 77 QRS -4 T 79 Sinus tachycardia, rate 104 bpm. Normal PR interval Possible Left atrial enlargement Septal infarct, age undetermined tj CC: Dr. A. Cheema Room Tech Req MD: Ref MD: NIK DR CHEEMA - ABNORMAL ECG - Confirmed By: Tony Jackson 08/26/ :58:44 I avr V1 V4 II avl V2 V5 III avf V3 V6 II GE MAC35 25 mm/sec 10 mm/mv F 60~ Hz

4 Case 1

5 Case 1 Angiogram normal Management: Admitted to hospital Diuretics, ACE inhibitor, β-blocker, Spironolactone, thiamine

6 Definition An inability for the heart to maintain sufficient blood flow to meet the metabolic requirements of the body, or to do so only at a raised filling pressure.

7 An inability for the heart to maintain sufficient blood flow to meet the metabolic requirements of the body

8 or to do so only at a raised filling pressure.

9 Definition Clinical syndrome characterised by diminished effort capacity and dyspnoea due to cardiac dysfunction.

10 Compensatory Mechanisms Frank-Starling Mechanism a. At rest, no HF b. HF due to LV systolic dysfunction c. Advanced HF

11 Compensatory Neurohormonal Stimulation Decreased Cardiac Output Sympathetic nervous system Renin-angiotensin system Antidiuretic hormone (vasopressin) Contractility Heart Vasoconstriction Circulating volume rate Anteriolar Venous Maintain blood pressure Venous return to heart ( preload) + Cardiac output + Stroke volume - Peripheral edema and pulmonary congestion

12 Compensatory Mechanisms Frank-Starling Mechanism a. At rest, no HF b. HF due to LV systolic dysfunction c. Advanced HF

13 Diagnosis History & clinical examination Blood tests (esp TFT, ferritin) ECG CXR Echocardiogram Angiography, cardiac catheterisation MRI

14 Diagnosis History & clinical examination Blood tests (esp TFT, ferritin) ECG CXR Echocardiogram Angiography, cardiac catheterisation MRI

15 Management Address underlying cause Correct ischaemia, repair/replace valves etc Non-pharmacological Avoid toxins Sodium & fluid restrict Exercise

16 Aetiology Ischaemia Post-viral myocarditis Hypertension Valvular Idiopathic - incl genetic Nutritional eg Beri-beri Toxins esp alcohol Metabolic haemochromatosis, Gaucher s Peripartum Tachycardiomyopathy Thyrotoxicosis HOCM Restrictive Constrictive pericarditis Rare eg non-compaction

17 Management Lifestyle Modifications: Weight reduction Discontinue smoking Avoid alcohol and other cardiotoxic substances Exercise Medical Considerations: Treat HTN, hyperlipidemia, diabetes, arrhythmias Coronary revascularization Anticoagulation Immunization Sodium restriction Daily weights Close outpatient monitoring

18 Management Pharmacological Diuretics ACE inhibitors ARB s β-blockers Spironolactone Digoxin Ivabradine

19 Preload reduction Diuretics Nitrates

20 Compensatory Mechanisms Frank-Starling Mechanism a. At rest, no HF b. HF due to LV systolic dysfunction c. Advanced HF

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22 Case 1 β-blocker uptitration limited by hypotension Ivabradine started

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24 Case 2 Mr B.J. 76 years Presents with progressive dyspnoea for a few months No angina, no history of hypertension, no recent infective illness, little alcohol Admitted to hospital with heart failure. Oedema, JVP elevated, heart rate 100 bpm, regular, BP normal. No murmurs

25 Case 2 - investigations Blood tests unremarkable TSH, ferritin

26 Case 2 - investigations

27 ECG Case 2 - investigations

28 Case 3 - investigations

29 Case 4 - investigations

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32 Case 2 - management Diuretics ACE inhibitor Spironolactone β - blocker Aspirin Statin ACE-I & β blocker uptitration limited by hypotension Symptomatic improvement but LVEF remained at 24%, NYHA FC II

33 Afterload reduction Concept evolved in 1970 s Sodium nitroprusside Phentolamine Nitrates Hydralazine

34 642 men with heart failure Randomised to Isosorbide mononitrate & Hydralazine vs Prazosin vs placebo 36% relative mortality risk reduction at 3 years (36% vs 47%)

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36 253 patients, NYHA FC IV Placebo vs Enalapril Mortality risk reduction at 6 months showed a 40% relative risk reduction (26% vs 44%)

37 7601 patients with heart failure Candesartan vs placebo (patients who tolerated ACE-I were taking them 10% relative risk reduction at 38 months

38 3023 patients, NYHA II IV, EF >40% No effect on mortality, reduced hospital admissions

39 2548 patients, NYHA II IV, EF <40% 15% relative risk reduction in composite outcome of death or hospital admission for heart failure.

40 2028 patients, ACE intolerant 23% relative risk reduction in death/hospital admission for heart failure

41 β-blockers MERIT-HF CIBIS Carvedilol SENIORS

42 Carvedilol 1094 patients, LVEF <35% Assigned 2:1 to Carvedilol or placebo 65% relative risk reduction (3.2% vs 7.8%) in death at 6 to 12 months

43 Bisoprolol 2647 patients, LVEF <35%, NYHA III or IV Bisoprolol or placebo 34% relative risk reduction (11.8% vs 17.3%) in mortality at 1.3 years

44 Metoprolol 3991 patients, LVEF <40%, NYHA II to IV 34% relative risk reduction (7.2 vs 11%) in mortality at 1 year

45 Nebivolol 2128 patients, >70 years, admission in 12 months prior or LVEF<35% Nebivolol vs placebo 14% relative risk reduction (31.1 vs 35.3%) in death/hf hospitalisation at 21 months

46 Aldosterone antagonists Spironolactone Eplerenone

47 Spironolactone 1663 patients, severe heart failure, LVEF <35% Spironolactone 25 mg vs placebo 30% relative risk reduction (35 vs 46%) in death at 24 months

48 Eplerenone 2737 patients, NYHA II, LVEF <35% Eplerenone (up to 50 mg) vs placebo 37% RR reduction (18 vs 26%) in death/hf hosp at 21 months

49 Digoxin 6800 patients, LVEF < 45% Digoxin 250 μg daily vs placebo No effect on mortailty (OR 0.99), 6% fewer hospitalisations at 37 months

50 Inotropes Increase mortality but sometimes needed for decongestion and symptom relief.

51 CRT Case 2 - management

52 Cardiac resynchronisation therapy

53 Cardiac resynchronisation therapy

54 ECG s pre & post Case 2 - management

55 Case 2 - management

56 Case 2 - management BP improved Beta-blocker uptitrated to target ACE-I increased to ½ target Asymptomatic

57 Case 3 Mrs J.H. 86 years IHD PCI s to RCA & left main Develops heart failure with persistent atrial fibrillation Cardioversion & Sotalol, later Amiodarone

58 Case 3 Syncope with pauses Pacemaker

59 Case 3

60 Case 4 Mrs M.J. 85 years Admitted with heart failure NYHA FC III No angina Hypertension, hyperlipidaemia Long-term steroid therapy for PMR

61 Case 4 PID: /14/ :14:10 JONES, MIRIAM 08/15/1927 DOB 85 years Female Dept Rx: Dx: Rate 70 PR 152 QRSD 130 QT 432 QTc AXIS-- P 62 QRS -28 T 93 Normal sinus rhythm with sinus arrhythmia, rate 70 bpm Right bundle branch block Minimal voltage criteria for LVH, may be normal variant Septal infarct, age undetermined TJ Room Tech Req MD: Ref MD: SE MEKEL, HARRIS - ABNORMAL ECG - Unconfirmed Study 00// 00:0: I avr V1 V4 II avl V2 V5 III avf V3 V6 II GE MAC35 25 mm/sec 10 mm/mv F 60~ Hz

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63 Case 4 Medications: Candesartan, Rosuvastatin, Aspirin, Frusemide, ISMN, Carvedilol.

64 Coronary angiogram

65 Coronary angiogram

66 Case 4 PCI to LAD, complicated by VF arrest, successfully resuscitated.

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71 Prevalence HF Incidence and Prevalence Worldwide, 22 million 1 United States, 5 million 2 Incidence Worldwide, 2 million new cases annually 1 United States, 500,000 new cases annually 2 HF afflicts 10 out of every 1,000 over age 65 in the U.S. 2 Extrapolating to regional Victoria 22,000 1 World Health Statistics, World Health Organization, American Heart Association, 2002 Heart and Stroke Statistical Update.

72 Prevalence of HF by Age and Gender United States: Males Females Percent of Population Source: NHANES III ( ), CDC/NCHS and the American Heart Association

73 Projections of prevalence of cardiovascular disease in (USA) Year CAD crude prevalence, % HF crude prevalence, % All CVD* crude prevalence, % % Change *Includes hypertension, CAD, HF, stroke Heidenreich PA. Circulation 2011;123:

74 Left Ventricular Dysfunction Systolic: Impaired contractility/ejection Approximately two-thirds of heart failure patients have systolic dysfunction 1 Diastolic: Impaired filling/relaxation (EF < 40%) (EF > 40 %) 30% 70% Diastolic Dysfunction Systolic Dysfunction 1 Lilly, L. Pathophysiology of Heart Disease. Second Edition p 200

75 Economic burden of Chronic Heart Failure Primary Care Post-discharge outpatient visits 2% 6% 5% Outpatient referral Hospital admissions Drug treatment Hospitalisation accounts for most CHF-associated costs Stewart S, et al. Eur J Heart Fail 2002;4: NHS data, United Kingdom

76 Ivabradine

77 Elevated HR at discharge is a predictor of one-year mortality in HF patients (OFICA) N=1658 (170 hospitals); median HR at discharge 71 bpm; 1 year mortality: 33% 41% Logeart D, et al. Eur Heart J 2012;33 - Abstract Supplement 485

78 Patients Audit of 100 CHF consecutive patients*, >50% had heart rate >70bpm 53.4% HR > 70 bpm 20.3% HR > 80 bpm (N=20) (N=54) *sinus rhythm, EF < 40%, completed β-blocker uptitration [n=54] or intolerant of a β-blocker [n=20] Heart rate Cowie MR and Davidson L. Int J Clin Pract 2012; 66: Reproduced with permission from M. Cowie, Royal Brompton Hospital, UK

79 Analysis restricted to patients for whom the specialty of the first BB supply was known Source: Data from PBS 10% sample, Department of Human Services (CO8526)

80 Systolic Heart Failure treatment with the I f Inhibitor Ivabradine Trial Swedberg K, et al. Lancet. 2010;376:875-85

81 Background Elevated heart rate is associated with poor outcome in a number of cardiovascular conditions including heart failure Heart rate remains elevated in many heart failure patients despite treatment by beta-blockers Ivabradine is a novel heart rate-lowering agent acting by inhibiting the I f current in the sino-atrial node

82 Primary objective To evaluate whether the I f inhibitor ivabradine improves cardiovascular outcomes in patients with 1.Moderate to severe chronic heart failure 2.Left ventricular ejection fraction 35% 3.Heart rate 70 bpm and 4.Optimised background therapy Swedberg K, et al. Lancet. 2010;376:875-85

83 Patients and follow-up 7411 screened 6558 randomized 3268 to ivabradine 3290 to placebo Excluded: 27 Excluded: analysed 2 lost to follow-up 3264 analysed 1 lost to follow-up Median study duration: 22.9 months; maximum: 41.7 months Swedberg K, et al. Lancet. 2010;376:875-85

84 Study endpoints Primary composite endpoint Cardiovascular death Hospitalisation for worsening heart failure Other endpoints All-cause, CV and HF death All-cause, CV and HF hospitalisation Composite of CV death, hospitalisation for HF or non fatal MI NYHA class / Patient & Physician Global Assessment Swedberg K, et al. Lancet. 2010;376:875-85

85 Patients (%) Chronic HF background treatment Ivabradine Placebo n= 3241 n= Beta-blockers ACEIs and/or ARBs Diuretics Aldosterone antagonists Digitalis 3 4 ICD/CRT Swedberg K, et al. Lancet. 2010;376:875-85

86 Study Baseline HR, bpm ACEI/ARB, or total, % BB, % Diuretics, % Antialdost antag, % CONSENSUS 1987 (n=253) 80 ST SOLVD 1991 (n=2569) 80 ST 7 85 NA MERIT HF, 1999 (n=3991) ST 91 NA CIBIS II, 1999 (n=2647) ST 99 NA COPERNICUS, 2001 (n=2289) ST RALES 1987 (n=253) ST CHARM Added, 2003 (n=2548) 73 ACE+ ST SENIORS, 2005 (n=2128) ST HEAAL, 2009 (n=3846) 71 ST SHIFT, 2010 (n=6505) References supplied upon request.

87 Mean heart rate reduction of 8 bpm with ivabradine Heart rate (bpm) Placebo Ivabradine weeks Months Swedberg K, et al. Lancet. 2010;376:875-85

88 Ivabradine reduced composite of CV death and hospitalisation for worsening HF Event Rate (%) % RRR p< Placebo Ivabradine 20 Lines separate by 3 months NNT = Months n=6505 Swedberg K, et al. Lancet. 2010;376:875-85

89 Effect of ivabradine in pre-specified subgroups n=6505 Age <65 years 65 years Sex Male Female Beta-blockers No Yes Aetiology of heart failure Non-ischaemic Ischaemic NYHA class NYHA class II NYHA class III or IV Diabetes No Yes Hypertension No Yes Baseline heart rate <77 bpm 77 bpm Test for interaction NS NS NS NS NS NS NS P = Hazard ratio Favours ivabradine Favours placebo 1.5 Swedberg K, et al. Lancet. 2010;376:875-85

90 Ivabradine reduced the composite of CV death and hospitalisation for worsening HF in patients with a heart rate >77bpm n=3357 Coralan Approved Product Information

91 Treatment effect on the primary composite endpoint, its components and secondary endpoints in patients with a heart rate >77bpm Coralan Approved Product Information

92 Ekman et al EHJ 2011: 32; 2395

93 HR reduction according to B-blocker dose and HR category HR reduction from baseline to 28 days with ivabradine* (bpm) 75 to <80 72 to <75 Baseline HR category (bpm) to <87 *Placebo corrected No BB BB<25% BB 25-50% BB % BB 100% Beta-blocker category No impact of BB dose on HR reduction with ivabradine Swedberg K, et al. J Am Coll Cardiol <72 Impact of baseline HR on HR reduction with ivabradine n=6398

94 Recommended in Australian Heart Failure guidelines TGA indication stipulates HR >77bpm

95 Ivabradine - The first selective heart rate lowering agent 1,2,3 In the sinus node, the I f current determines the slope of diastolic depolarisation, the frequency of action potentials & thus heart rate 1,2 Adapted from reference 1 & Thollon C, et al. Br J Pharmacol. 2007;150: DiFrancesco A, et al. Drugs. 2004;64: Coralan Approved Product Information *Please refer to Coralan Approved Product Information before prescribing.

96 Surgery STITCH CABG Valve surgery

97 Management Device therapy ICD for poor LV function Cardiac resynchronisation therapy + ICD LV assist devices Cardiac transplantation

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100 Cardiac resynchronisation therapy

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102 Treatment Approach for the Patient Stage A At high risk, no structural disease with Heart Failure Stage B Structural heart disease, asymptomatic Stage C Structural heart disease with prior/current symptoms of HF Stage D Refractory HF requiring specialized interventions Therapy Therapy Therapy Therapy Treat Hypertension Treat lipid disorders Encourage regular exercise Discourage alcohol intake ACE inhibition All measures under stage A ACE inhibitors in appropriate patients Beta-blockers in appropriate patients All measures under stage A Drugs: Diuretics ACE inhibitors Beta-blockers Digitalis Dietary salt restriction All measures under stages A,B, and C Mechanical assist devices Heart transplantation Continuous (not intermittent) IV inotropic infusions for palliation Hospice care Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult, 2001

103 AF rate control

104 Effect of stopping alcohol excess

105 The Vicious Cycle of Heart Failure Management Chronic HF Diurese & Home SOB Weight Hospitalization IV Lasix or Admit Emergency Room PO Lasix MD s Office

106 HFpEF Common + 50% Increases with age, Commoner in women Commoner with history of hypertension Prognosis as poor as HFrEF Mainstay of treatment is diuretics and BP control

107 HFpEF

108 Remote monitoring

109 OSA & heart failure Commonly co-exist. Up to 30% of patients with heart failure have OSA

110 Refractory heart failure Sequential nephron blockade

111 Specific challenges Managing complications AF, renal dysfunction Anticoagulation Warfarin vs NOAC s End-of-life care

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114 Summary Heart failure is common and a large burden on healthcare Don t forget the echocardiogram Look for reversible causes Fine-tune the medications Consider device therapy Involve the patient