1. Heart Failure Workshop Dr Steven Little Consultant Cardiologist RBH

2. Agenda Use of BNP Importance of optimal medical therapy Importance of heart rate control Heart failure and renal impairment Heart failure and low BP Case study

3. Role of BNP Secreted by cardiomyocytes in response to stretching Low BNP felt to have high negative predictive value (>100 pg/ml sensitivity 90%, specificity 76%) High BNP (>400pg/ml) has stronger positive predictive value and conveys worse prognosis if heart failure confirmed

5. Potential confounders Raise BNP LVH Ischaemia Tachycardia RV strain Hypoxaemia GFR < 60ml/min Age > 70 years COPD Sepsis Liver cirrhosis Anaemia Lower BNP Diuretics ACE-inhibitors/ARBs Beta-blockers Spironalactone/Eplerenone Obesity

6. Importance of optimal medical therapy Before 1990, the era of modern medical treatment, 60-70% of patients dead within 5 years of diagnosis Prognosis has improved with modern medical therapy but 1 year mortality rates remain higher than for most cancers

8. Optimal Medical Therapy

9. Real world experience

10. Beta-blockers in particular have historically been under-prescribed

11. Heart rate control Higher heart rates known to be associated with poorer prognosis in heart failure Patients can develop LV dysfunction in response to persistent tachycardia which often improves with rate control Previously unclear if this was cause or effect

12. SHIFT study EF < 35% NYHA II-IV On maximal tolerated dose or intolerant of beta-blocker SR Resting HR > 70 bpm

14. Mortality benefits of ivabradine in heart failure patients with heart rate ≥75bpm 1-2 1. PROCORALAN Summary of Product Characteristics. / 2. Data on file 12MDA0004 SHIFT endpoint analysis HR≥75bpm / 3. Data on file 12PRC0011 SHIFT baseline characteristics HR≥75bpm On top of guideline-based treatment ≥75bpm 1.10.40.50.60.70.80.91.0 Cardiovascular death -17% ARR 2.6% HR 0.83 p=0.0166 NNT 38 All cause mortality -17% ARR 2.8% HR 0.83 p=0.0109 NNT 36 Death from heart failure -39% ARR 2.2% HR 0.61 p=0.0006 NNT 45 HR (95% CI) Favours ivabradine Favours placebo Primary composite end point -24% ARR 6.2% HR 0.76 p<0.0001 NNT 16 * Numbers needed to treat Subgroup of patients from the main SHIFT cohort with heart rate ≥75bpm Study duration 21.5 months 3 n=4 150 Primary endpoint: Cardiovascular death or hospitalisation for worsening heart failure NNTs* over duration of the study

15. Prescribing in renal impairment and hypotension Patients with cardiac failure often have renal impairment and low BP Tends to be exacerbated by prognostically important medication Renal impairment and low BP marker for poor prognosis- clinical deterioration often precipitated by withdrawal of these agents

16. ACE-Inhibitors Contra-indications – History of angioneurotic oedema – Bilateral renal artery stenosis Cautions (seek specialist advice) – Hyperkalaemia (k+ > 5mmol/L) – Significant renal dysfunction (creatinine > 221μmol/L, GFR < 30ml/min) – Symptomatic hypotension or severe asymptomatic hypotension (BP < 90mmHg)

17. Check U&Es 1-2 weeks after initiation and up-titrations of ACE-I Some rise in urea, creatinine and potassium to be expected after initiation of an ACE-I An increase in creatinine of up to 50% from baseline or 266μmol/L (GFR <25ml/min), whichever is smaller, is acceptable An increase in potassium to 5.5mmol/L is acceptable If creatinine/potassium do rise excessively consider stopping concomitant nephrotoxic drugs (eg. NSAIDS), potassium supplements/sparing agents (spironalactone,eplerenone) and reducing diuretic dose if no congestion

18. If greater rises in creatinine/potassium persist despite adjustment of concomitant medication half the dose and repeat bloods in 1-2 weeks; if there is still an unsatisfactory response seek specialist advice If creatinine rises greater than 100% from baseline or to >310 μmol/L (GFR < 20ml/min) stop and seek specialist advice NB it is very rarely necessary to stop an ACE-Inhibitor and clinical deterioration is likely if treatment is withdrawn

19. Mineralocorticoid receptor antagonists (MRAs) Cautions (seek specialist advice) – Significant hyperkalaemia (K+ > 5mmol/L) – Significant renal dysfunction (creatinine > 221μmol/L, GFR <30ml/min) If potassium rises above 5.5mmol/L or creatinine to 221μmol/L, GFR < 30ml/min reduce dose to 25mg alternate days and monitor bloods closely If potassium rises to above 6mmol/L or creatinine above 310μmol/L stop and seek specialist advice

20. Nitrates/hydralazine Combination of long acting nitrates and hydralazine shown to be beneficial in heart failure pre ACE-Inhibitors Subsequently shown to be inferior to ACE- Inhibitors Have been shown to offer symptomatic and prognostic benefits on top of ACE-Inhibitors in African-Americans Valid alternative to ACE-Inhibitors/ARBs in patients who are genuinely intolerant

21. Low BP Asymptomatic hypotension doesn’t usually require any change in therapy If dizzyness and/or confusion and low BP reconsider need for nitrates, calcium channel blockers and other vasodilators If no congestion consider reducing diuretic dose then ACE-Inhibitor dose If these measures don’t solve problem seek specialist advice

22. Case study 60 male 2 month history exertional breathlessness and ankle oedema PMSH – Type II DM – Hypertension – Raised BMI – COPD (ex-smoker) – Trigeminal neuralgia DH – Metformin – Pioglitazone – Bendroflumethiazide – Verapamil – Simvastatin – Gabapentin – Inhalers

23. Initial investigation Hb 111 Na+ 130, K+ 4.7, U 8.0, Cr 113 BNP 1009 Referred to Direct Access Echocardiogram/Cardiology Review

24. Direct Access Clinic Breathless mobilising short distances (NYHA III) Drinking 70 units alcohol/week Pulse 100 bpm BP 100/60mmHg JVP raised Reduced air entry bi-basally Bilateral oedema to thighs Echo- Severe LV dysfunction ECG- Sinus tachycardia, left bundle branch block CXR- Large heart, bi-basal effusions

25. Initial management Advised to reduce alcohol intake Verapamil, pioglitazone and gabapentin stopped Bendrofluazide swopped to furosemide 80mg od Ramipril 2.5mg od added Bisoprolol 1.25mg od added 4 week F/U appointment arranged in cardiology clinic

26. 3 months later On furosemide 80mg od, ramipril 10mg od and bisoprolol 10mg od Symptoms much improved (NYHA II) No longer oedematous Pulse 80 bpm and regular BP 105/60mmHg