Heart Failure Update. Chim Lang

Transcription

1 Heart Failure Update Chim Lang

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3 Heart Failure Patient s Journey Acute Treat and stabilize Initiate monitoring Plan interventions Chronic Optimize drug and device therapy Manage Co-morbidities Subacute Monitoring Diagnosis Initiate chronic treatment Additional diagnostics Perform indicated procedures End of Life Symptomatic treatment Plan long term care Adapted from ESC guidelines 2012

4 BNP testing in Tayside: At last! Patient will be offered an urgent appointment to advanced heart failure clinic and patient will be offered an urgent echo prior to clinic both within 2 weeks of BNP result. NT-proBNP > 2000 ICE result will be available for GP with guidance for Rx in the interim. Patient will progress to the standard echo waiting list. Please note that echo waits are currently approximately 9 months. NT-proBNP You may wish to start empirical treatment in the interim based on clinical judgement. ICE result will be available for GP with guidance. NT-proBNP <400 Patient will be removed from the echo waiting list as echo not indicated. Ongoing management in primary care. ICE result will confirm removal from echo waiting list.

5 BNP testing in Tayside: A Success! (Oct 17 Mar18)

6 BNP: Prognostic marker

7 How does it guide management? You will still try and optimize therapy in all patients

8 Heart Failure Patient s Journey Acute Treat and stabilize Initiate monitoring Plan interventions Chronic Optimize drug and device therapy Manage Co-morbidities Subacute Monitoring Diagnosis Initiate chronic treatment Additional diagnostics Perform indicated procedures End of Life Symptomatic treatment Plan long term care Adapted from ESC guidelines 2012

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11 Hydrallazine plus Nitrates Patients with poor renal function and cannot tolerate ACEI/ARB Hydrallazine Start at 25 mg tid; titrate up to 100 mg tid Isosorbide dinitrate 40 mg tid

12 Devices

13 ICDs in CHF Current guidelines rely heavy on SCD-HeFT ; ; 69% BB, 20% MRA

14 DANISH Study N=556 DCM pts. 96% BBs. 58% CRT. Kober L et al. NEJM 2016; 375:

15 Random-effects meta-analysis evaluating the effect of ICD therapy on all-cause mortality in patients with non-ischaemic cardiomyopathy. Farid Foroutan et al. Heart doi: /heartjnl Copyright BMJ Publishing Group Ltd & British Cardiovascular Society. All rights reserved.

16 Summary forest plot of subgroup analyses for all-cause mortality. Amr F Barakat et al. BMJ Open 2017;7:e by British Medical Journal Publishing Group

17 ICD in DCM Appropriate shock rates have decreased Vary widely with age and co morbidities Large number of patients never receive appropriate shocks Many die prior to ICD therapy (because non arrhythmic death outweighs)

18 LCZ696:First in Class ARNI Dual Acting Inhibitor of RAAS and Neprilysin Enzyme ARNI=angiotensin receptor neprilysin inhibitor Neprilysin inhibitor (NEPi) To enhance effects of Natriuretic Peptides (NP) NEP inhibitor Vasodilation Blood pressure Sympathetic tone Aldosterone levels Natriuresis/Diuresis Angiotensin Receptor Blocker (ARB) To block Renin Angiotensin Aldosterone System (RAAS) Valsartan Vasodilation Blood pressure Sympathetic tone Aldosterone levels Cellular growth Natriuresis NEPi = neprilysin inhibitor, ARB = angiotensin receptor (AT1) blocker, NP = natriuretic peptides 82 PARAGON-HF (CLCZ696D2301) CRA Training June 2013 Business Use Only

19 PARADIGM-HF: Cardiovascular Death or Heart Failure Hospitalization (Primary Endpoint) Kaplan-Meier Estimate of Cumulative Rates (%) Patients at Risk LCZ696 Enalapril 8 0 Enalapril (n=4212) Days After Randomization LCZ696 (n=4187) HR = 0.80 ( ) P = Number needed to treat =

20 Doses of Entresto Entresto 24 mg/26 mg TWICE DAILY (for ACEI naïve patients or those on low dose ACEI (ramipril 2.5 mg) /ARB (losartan 50 mg) Entresto 49 mg/51 mg TWICE DAILY (from high dose ACEI (Ramipril 10 mg) or ARB (losartan 150 mg) Target dose Entresto 97 mg/103 mg TWICE DAILY

21 Heart Failure with Preserved Ejection Fraction 85

22 HFpEF: Increasing prevalence Presentation Title Presenter Name Date Subject Business Use Only 86

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25 Effect of exercise training in HFpEF. Ambarish Pandey et al. Circ Heart Fail. 2015;8:33-40

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27 HFpEF:? Metformin Lam CS. Eur Heart J. 2018;39(30): doi: /eurheartj/ehy301

28 MET-HFpEF Study Proposal Ify Mordi, Graham Rena, Chim Lang Naveed Sattar, John McMurray, Mark Petrie Calvin Chin, Carolyn Lam

29 Patient s journey Acute heart failure Diagnosis and investigations Optimization of HF therapy Monitoring Co-morbidities Anaemia Diabetes Future therapies

30 Ten Most Common Co-morbidities in HF (N=4,947,918), 2011 J Am Coll Cardiol. 2013;62(16):e147-e239

31 Anemia in patients with heart failure Hb = hemoglobin Hct = hematocrit HF = heart failure The prevalence of anemia in heart failure patients is approximately: 30% for Inpatients 20% for Outpatients

32 Evidence to support treatment of anemia van Veldhuisen, D. J. et al. (2011) Anemia and iron deficiency in heart failure: mechanisms and therapeutic approaches Nat. Rev. Cardiol. doi: /nrcardio

33 Noticed an improvement in intravenous iron, compared to placebo (note: scale is between metres). The 6 minute walk test aims to improve exercise tolerance and perception of symptomology.

34 IRONMAN study Outcome Trial First RCT looking at the effect of intravenous iron, Monofer (iron isomaltoside 1000, 10%), on CHF patients patients with iron deficiency and CHF due to left ventricular (LV) systolic Randomisation: 1:1 ratio to either the active treatment (IV iron, Monofer) or the standard therapy group. Primary endpoint: CV mortality or hospitalisation for worsening HF

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36 CHF and mortality in diabetics 5-yr survival rate 80% vs 12.5% (Bertoni AG et al. Diabetes Care 2004; 27: )

37 HbA1c and Outcome in T2D and HF: Existence of a Sweet Spot Elder DHJ et al. Eur J Heart fail 2015; 18(1):94-102

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39 30% lower risk of mortality in metformin users HR, 0.67 (95% CI ). Evans J et al. Am J Cardiol 2010

40 Metformin in CHF: Meta analysis of 34,000 patients Associated with reduced mortality (pooled adjusted risk estimates: 0.80; ; I(2)=15%; P<0.001). Metformin was associated with a small reduction in all cause hospitalizations (pooled adjusted risk estimate: 0.93; ; I(2)=0%; P=0.01) Eurich D et al. Circ Heart Fail 2013 May;6(3):

41 Impact on Global Guidelines American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular and Stroke Nursing; Council on Hypertension; and Council on Quality and Outcomes Research. Contributory Risk and Management of Comorbidities of Hypertension, Obesity, Diabetes Mellitus, Hyperlipidemia, and Metabolic Syndrome in Chronic Heart Failure: A Scientific Statement From the American Heart Association. Circulation Dec 6;134(23):e535 e578. (Ref 145) Bocchi EA. Et al. Updating of the Brazilian guideline for chronic heart failure 2012]. Arq Bras Cardiol 2012; 98 (1 Suppl 1) (Ref 222)

42 Thiazolidinediones Potent insulin sensitizer Off Target Effects Fluid retention and weight gain (1-3 kg) Increased incidence of CHF ADA/ AHA consensus statement Should not be used in patients with NYHA III/IV HF

43 SGLT2 Inhibition Less glucose reabsorbed SGLT2 inhibitors Urinary glucose excretion CV Risk Factor Reduction Lowers blood glucose levels Lowers BP via osmotic diuresis Increases urinary caloric loss with reductions in body weight Reduces albuminuria possibly due to alterations in tubuloglomerular feedback

44 Nassif, M. & Kosiborod, M. (2018) Effect of glucose-lowering therapies on heart failure Nat. Rev. Cardiol. doi: /nrcardio

45 Which patient groups? HF patients At risk HF patients? HFrEF vs HFpEF?

46 Minority ( 10%) of patients had HF in EMPA REG and CANVAS

47 What and how? Mechanisms of benefit?

48 Cardiovascular Effects of SGLT inhibitors Research into the EFfect Of SGLT2 inhibition on left ventricular Remodelling in patients with heart failure and diabetes Mellitus (REFORM) LV volumes Exercise capacity NCT

49 Does Dapagliflozin Regress Left Ventricular Hypertrophy In Patients With Type 2 Diabetes? (DAPA LVH) NCT

50 Renal and Cardiovascular Effects of SGLT2 inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure. (RECEDE CHF) A randomised control crossover study

51 Summary Significant advances in HF therapy that is underpinned by a pivotal RCTs Need more trials in acute HF and HFpEF