258 - Heart Failure: Management Flashcards
Challenges in HFpEF and general principles of treatment of HFpEF
Most drugs for HFrEF were unable to demonstrate mortality reduction benefits in HFpEF, only reduction in HF hospitalisation (2023)
- ARB
- Digoxin
- Beta blockers
- ARNI
Management of HFpEF focused on:
1. Improving symptoms and effort tolerance
2. Lifestyle modification
3. Control of congestion
4. Stabilisation of heart rhythm
5. Control of BP to guideline-recommended target (most effective)
6. Management of comorbidities
Angiotensin Receptor Blockers Trial in HFpEF
- Candesartan in HFpEF - Assessment of Mortality and Morbidity (CHARM)
- Irbesartan in HFpEF (I-PRESERVE)
- Perindopril in Elderly People with CHF (PEP-CHF)
Candesartan (CHARM)
Significant reduction in HF hospitalisation
No difference in all-cause mortality
Irbesartan (I-PRESERVE)
No difference in composite of CVS death or HF hospitalisation
Perindopril (PEP-CHF)
Probable early benefits, but accentuated over longer duration follow up
Digoxin Investigation Group (DIG) Ancillary Trial on HFpEF
No impact of digoxin on all-cause mortality or CVS hospitalisation among patients with chronic HF, EF > 45% and sinus rhythm
Modest reduction in HF hospitalisation
Beta Blockers in HFpEF
- No dedicated study of beta blockers
- Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors with Heart Failure (SENIORS)
Nebivolol (SENIORS)
Vasodilating beta blockers did not significantly reduce all cause or CVS mortality
MRA trials on HFpEF
- Treatment of Preserved Cardiac Function Heart Failure with Aldosterone Antagonist (TOPCAT)
- Aldosterone Receptor Blockage in Diastolic Heart Failure (ALDO-DHF)
- Future studies: SPIRRIT-HFpEF, FINE-ARTS-HF underway (no result yet)
TOPCAT
No improvement in endpoint of CVS death, aborted cardiac arrest
Reduction in HF hospitalisation
ALDO-DHF
Spironolactone improved TTE indices of diastolic dysfunction
Failed to improve exercise capacity, symptoms or QOL
Novel targets (nitric oxide pathway) trial on HFpEF: sildenafil, nitrates
- PDE5-i to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure (RELAX)
- Nitrates Effect on Activity Tolerance in HFpEF (NEAT-HFpEF)
- Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF (INDIE-HFpEF)
Sildenafil (RELAX)
No improvement in functional capacity, QOL or other parametrys
ISMN (RELAX)
No improvement in QOL or submaximal exercise capacity
Decreased overall activity levels in treated patients
Inorganic nitrate (INDIE-HFpEF)
Enhances NO signalling however no improvement in functional capacity
ARNI trials in HFpEF
- Neprilysin inhibtion increases circulating __ to facilitate CGMP signaling, which enhances __, reduces __
- PARAGON-HF
Vasoactive peptides (natriuretic peptides)
Enhances myocardial relaxation
Reduces ventricular hypertrophy
Entresto (PARAGON-HF)
13% reduction in rate of primary composite endpoint (QOL, NYHA, renal function), however narrowly missed statistical significance (p=0.06)
SGLT2i Trials in HFpEF
-DAPA DELIVER
- EMPEROR-PRESERVED
Dapagliflozin (DELIVER)
Reduces CVS mortality and HF hospitalisation
Empagliflozin (EMPEROR-PRESERVED)
3% reduction in CVS death or HF hospitalisation
Prognosis of ADHF
50% re-admissions within 6 months
5% short term (in-hospital) mortality
20% long term cardiovascular mortality at 1 year
Causes/precipitating factors of acute decompensation of heart failure
- Non-compliance to medication
- Dietary salt or fluid indiscretion
- Acute illness, infection or inflammation
- New medications: NSAIDs, thiazolidinediones, TNF-i, anti-depressants, cancer therapies, flu meds with cardiac stimulants
- Pulmonary embolism
- Arrhythmias
What are the parameters associated with worse outcomes in ADHF?
- Urea > 15 mmol/L
- Creatinine > 243 umol/L
- SBP < 115mmHg
- Elevated cardiac biomarkers - troponin, BNP
Treatment of symptomatic HFrEF
- Renocentric (diuresis)
- Haemodynamic (digoxin, inotropic)
- Neurohormonal antagonism (disease modifying)
ACEIs and ARBs in HFrEF
- mechanism? not done
- High vs low dose trials: ACEIs (ATLAS), ARBs (HEAAL)
ACEi confers 23% reduction in mortality and 35% reduction in combined endpoint of mortality and hospitalitsation in HFrEF
ARBs are suitable alternatives for ACEi intolerance (cough, angioedema)
ATLAS and HEAAL Dosing trials
Higher dose has lower dates of death and HF hospitalisation
In the absence of hypotension (fatigue, giddiness), aim to uptitrate every 2 weeks as tolerated
Beta blockers in HFrEF
- mechanism? not done
- High vs low dose beta blocker trial (MOCHA)
Does not exhibit class effect - BBs with intrinsic sympathomimetic activity do not demonstrate survival benefits.
Limited to: metoprolol, bisoprolol, carvediolol
MOCHA dosing trial
Higher dose has lower dates of death and HF hospitalisation
In the absence of hypotension (fatigue, giddiness), aim to uptitrate every 2 weeks as tolerated
Cardiac Insufficiency Bisoprolol Study (CIBIS)
- Which to start first? beta blockers or ACEIs?
No significant difference in outcoms based on sequence of drug initiation
Important to optimally titrate doses of medication
