Heart failure

what is heart failure

heart cannot pump blood efficiently

• symptoms: breathlessness, ankle swelling, and fatigue that may be accompanied by signs (elevated jugular venous pressure, pulmonary crackles, and peripheral oedema)

• It is due to a structural/functional abnormality of the heart → elevated intracardiac pressures/inadequate cardiac output at rest/during exercise

what are the causes of heart failure

• arrhrythmias 

• hypertension 

• ischaemic heart disease 

• cardiomyopathy (walls of the heart chambers have become stretched, thickened or stiff)

• congenital heart disease 

• valve disease 

• viral infection 

• medicines 

cardiac output equation

Cardiac Output (CO) L/min = Stroke Volume X Heart Rate

• stroke volume = Volume of blood pumped out of left ventricle

mean arterial pressure (MAP) equation

MAP = CO x TPR

• Cardiac output

• total peripheral resistance 

what is the pathophysiology of heart failure

reduced cardiac output → activation of RAS and SNS → salt and water retention / vasoconstriction / tachycardia / arrhythmias / myocyte changes 

• body tries to compensate for compromised cardiac output with activation of different neurohormonal pathways

  • renin-angiotensin system (RAS)

  • sympathetic nervous system (SNS)

• Although this seems logical, the net effect is increased heart workload with increased preload (venous return) and afterload (arterial resistance)

what changes in the heart occur in heart failure

Cellular and extracellular changes

• Myocyte loss

• Degradation of extracellular matrix

• Replacement by fibrosis (scarring)

Changes in size, shape and function

• Left ventricular dilation and increased left ventricular wall stress

• Change from prolate ellipse to sphere

• decreased contractility

what are other neurohormonal and compensatory mechanisms that cause heart failure 

• vasopressin hormone → vasoconstriction 

• natriuretic peptide → affect fluid balance 

• Frank-Starling law mechanism 

what is Starling’s law

link between stretching muscle and the force of contraction

• Observation that as pre-load increases (more stretching), ventricular output also increases (greater force of contraction)

• In heart failure, impaired contractile function means that even higher preload (more stretching) cannot increase ventricular output (force of contraction) to the same extent

how do myocytes lead to arrhythmias and sudden cardiac death 

failing myocytes have reduced calcium transients and electrophysiological abnormalities

• Reduced size of sarcoplasmic reticulum calcium store (due to reduced expression of sarcoplasmic reticulum Calcium pump)

• Upregulated sarcolemmal Na/Ca exchanger

• Downregulated Inward Rectifier K+ channel

• Prolonged action potential → arrhythmias and sudden cardiac death 
  • Disruption of the electrical conduction system

how does heart failure progress

• Start of heart failure

• Compensatory mechanisms

• Worsening of HF and development of symptoms

• Treatments

• Improvement in symptoms

• Acute decompensations, some recovery

• Gradual decline in quality of life  due to worsening symptoms

what is the classification for heart failure

• duration → chronic or acute 

• function → severity of symptoms classed by NYHA Class I–IV or ACC/AHA Stages A–D

• side → left: pulmonary symptoms or right: peripheral oedema 

• direction → forwards: inadequate discharge of blood into arterial system, backwards: inadequate filling of ventricles and discharge of contents, build up of backward pressure 

• pathophysiology → systolic: impaired ejection or diastolic: impaired filling

• ejection fraction: preserved HF_pEF or reduced HF_rEF

what is ejection fraction

shows how much blood leaves the left ventricle with each heartbeat

• expressed as %

• normal range is 50-70%

• borderline/mildly reduced range is 41-49%

• reduced range is less than 40%

• estimated using an echocardiogram 

what do the different ranges of EF mean

• Heart failure reduced EF (<40%)

  • Ventricles filling with blood but heart not pumping it out very well.

  • eg.ventricular remodelling/ myocyte damage post ACS, dilation of ventricles

• Heart failure with mildly reduced EF (41-49%)

• Heart failure preserved EF (50% or more)

  • Not enough blood coming into the ventricles (despite normal EF)

  • Eg.Valve issues, poor filling, hypertension, causing hypertrophy HFrEF ((heart failure with reduced ejection fraction) and HFpEF (heart failure with preserved ejection fraction)

what is the NHYA (New York Heart Association) functional classification to asses HF symptom severity

• Class I → no symptoms in normal physical activity

• Class II → mild symptoms in normal physical activity

• Class III → marked symptoms in normal physical activity, asymptomatic at rest only

• Class IV → severe symptoms, symptoms even at rest

what are the stage of heart failure according to ACC/AHA

• Stage A → at risk of heart failure

• Stage B → pre heart failure

• Stage C → symptomatic heart failure 

• Stage D → advanced heart failure 

what are the signs and symptoms of heart failure from clinical examination

• Raised JVP (Jugular Venous Pressure) → increased elevated right atrial pressure 

• Tachypnoea → rapid breathing 

• Hypotension

• Tachycardia → fast heart rate 

• Crepitations on chest auscultation → crackling sounds in lungs 

• Pallor → paleness

• Cachexia → severe weight and muscle loss

• Ascites → fluid in abdomen 

• Peripheral oedema → swelling in legs/ankles 

• Cyanosis → blueish discolouration of skin/lips

• Cold peripheries → cold hands/feet 

what are the signs and symptoms of heart failure reported by people

• Fatigue

• Confusion

• Dyspnoea → shortness of breath

• Orthopnoea → shortness of breath when lying down that's relieved by standing or sitting up

• Paroxysmal nocturnal dyspnoea (PND) → wake up suddenly feeling like you can't catch your breath

• Palpitations

• Dizziness

• Bloatedness/fullness

• Weight gain

• Reduction in exercise tolerance

• Nocturia → frequent weeing at night

how do you diagnose HF according to NICE guidelines

• The NT-proBNP (N-terminal pro–B-type natriuretic peptide) blood test is used as an initial screening test for heart failure.

• It measures a hormone released when the heart is under stress or strain

  • NT- pro BNP>2000ng/L → referral for within 2 weeks 

  • NT-pro BNP 400-2000ng/L → referral for within 6 weeks 

  • NT-pro BNP <400ng/L → less likely to be heart failure 

what are the aims of treatment

• improve mortality

• reduce symptoms

• reduce time spent in hospital

how can heart failure be managed

• Medicines for

  • HFpEF (Heart Failure with Preserved Ejection Fraction) 

  • HFrEF (Heart Failure with Reduced Ejection Fraction) 

  • HFmrEF (Heart Failure with Mildly Reduced Ejection Fraction)

• surgical procedures

• Manage any comorbidities or likely causes

what medicines work against compensatory mechanisms

• RAS mechanism → ACEI, Angiotensin II Receptor Blockers, Mineralocorticoid Receptor Antagonists

• SNS mechanism → beta blockers, ivabradine

• Vasoconstriction from vasopressin mechanism → vasodilators such as nitrates 

• naturetic peptides mechanism → neprolysin inhibitors 

  • Most medicines shown to be beneficial in HFrEF (heart failure with reduced ejection fraction)

  • Limited medicines with mortality benefit for HFpEF (heart failure with preserved ejection fraction)

what are the 4 pillar for treatment of Heart Failure with Reduced Ejection Fraction, HFrEF (EF less than 40%)

• Angiotensin Receptor-Neprilysin Inhibitors e.g. sacubitril/valsartan considered in symptomatic people despite first line max treatment with reduced EF (<35%)

• Mineralocorticoid Receptor Antagonists include eplerenone or spironolactone, but can cause gynaecomastia → consider switch to eplerenone

• SGLT2 inhibitors → lower blood glucose by increasing its excretion in urine

• IV iron → all HF patients should be regularly screened for anaemia and iron deficiency → given IV iron if appropriate

• diuretics → symptom control to remove water → don’t affect mortality

what are lifestyle changes you can change for heart failure

• weight management

• exercise

• cardiac rehabilitation

what are angiotensin converting enzyme inhibitors (ACEIs)

• examples: ramipril, analapril, perindopril 

• mechansim 

  • inhibition of ACE → block conversion of angiotensin I to angiotensin II

  • Decrease arterial and venous vasoconstriction

  • Decrease blood volume (no increase in sodium and subsequent water retention from aldosterone)

  • Decreased compensatory effects of RAAS

• effects: trials using enalapril show reduction in CV deaths, worsening HF, reduction in mortality overall

what are Angiotensin receptor blockers (ARBs)

• examples: candesartan, valsartan, irbesartan 

• mechanism 

  • Angiotensin 2 receptor antagonist → blocking the effect of angiotensin II

  • Decrease arterial and venous vasoconstriction

  • Decrease blood volume (no increase in sodium and subsequent water retention from aldosterone)

  • Decrease compensatory effects of RAAS

• effects: trials using candesartan and vaslartan showed most benefit seen when taken without an ACEI and more side effects when with ACEI

what are Angiotensin receptor neprilysin inhibitor (ARNI)

• examples: sacubitril and valsartan

• mechanism of sacubitril 

  • eprilysin breaks down natriuretic peptides

  • Sacubitril prevents breakdown of natriuretic peptides →  increased vasodilation, natriuresis and diuresis

what are Mineralocorticoid Receptor Antagonists (MRAs)

• examples: spironolactone and eplerenone 

• mechanism

  • Block action of aldosterone, decrease blood volume (no increase in sodium and subsequent water retention)

  • May affect vasoconstriction

  • Reduce some of the fibrosis and myocardial necrosis

what are beta blockers

• examples: bisoprolol, nebivolol and carvedilol 

• mechanism:

  • Beta-selective adrenoceptor blockers, block action of adrenaline and noradrenaline on heart, reducing sympathetic drive and opposing neurohormonal adaptation

  • Slows heart down → anti-arrhythmic effects

what are Sodium-glucose co-transporter-2 inhibitors (SGLT2i)

• examples: dapagliflozin and empagliflozin 

• mechanism → reduce reabsorption of glucose in kidneys, promoting urinary glucose excretion and reducing sodium reabsorption

• mechanism of action is unclear in heart failure, may be beneficial in 

  • diuresis 

  • blood pressure reduction 

  • prevention of cardiac remodelling

what can be used to manage symptoms from oedema

• loop diuretics

• thiazide and thiazide-like diuretics

what are loop diuretics

• examples: furosemide and bumetanide

• mechanism:

  • Alter how kidney handles sodium

  • Inhibit Na+/K+/2Cl- co-transporter in the loop of Henle in the kidney, preventing sodium reabsorption

  • Water follows sodium, so without sodium reabsorption water does not follow and diuresis results

what are thiazide and thiazide-like diuretics 

• examples: Bendroflumethiazide (thiazide), indapamide (thiazide-like), metolazone (thiazide-like)

• mechanism: 

  • • Alter how kidney handles sodium

  • Inhibit Na+/Cl- transporter in the distal convoluted tubule, preventing sodium reabsorption

  • Water follows sodium, so without sodium reabsorption water does not follow and diuresis results

why is digoxin used in heart failure

• mechanism:

  • Inhibits Na+/K+ ATPase → rise in intracellular sodium, promoting calcium entry → increased force of myocardial contraction (positive inotropic effect)

  • Impairs atrioventricular conduction (directly and indirectly via vagal activation), slowing heart down and controlling ventricular rate → anti-arrhythmic effects

• No mortality benefit, but there is reduction in hospitalisation and is used to improve symptoms

why is ivabradine used in heart failure

• reduces heart rate without reducing blood pressure

• mechanism

  • Blocks sinoatrial node pacemaker, sodium and potassium (i-funny (If) or ‘funny current’) currents, reducing heart rate and therefore oxygen demand of the heart

  • May cause visual disturbance due to retinal I_f

• commence and uptitrate beta blocker therapy to maximum tolerated dose before considering ivabradine

why is hydralazine used in heart failure

Mechanism:

• Precise mechanism of action not known, but works as a direct acting vasodilator

• Effect is a reduction in blood pressure

• Can cause sodium and fluid retention → need to monitor

why are nitrates used in heart failure 

mechanism: Vasodilation via the release of nitric oxide (NO)

why is IV iron used in heart failure

• patients need to be screened for low iron 

• UV iron used in those who are sympotamtic and other criteria 

what is the treatment for HFpEF, heart failure with preserved ejection fraction (EF ≥50%)

• Until recently treatment aimed at:

  • Symptom control with diuretics

  • Improved management of co-existing co-morbidities e.g. hypertension, ischaemic heart disease (see other lectures)

• However there are now mortality benefits for SGLT2 inhibitors such as Empagliflozin and dapagliflozin 

• there are reduced hospitalisation for MRAs

what do we need to monitor in heart failures

• Medicines → U&Es, FBC, blood pressure, heart rate

• Symptoms → important that patients monitor themselves and report any deterioration e.g. breathlessness, oedema, weight

how is acute heart failure managed

• IV loop diuretics

• Oxygen may be needed

• Other specialist treatments eg iv inotropes

• Treat any underlying cause

• May need to modify existing medicines

• Under specialist team

what are non-pharmacological managements for HF

• Valve replacement if appropriate

• Ablation (if secondary to arrhythmias)

• Cardiac resynchronisation therapy (device that can improve pumping function of heart, improve synchronicity of the ventricles)

• Implantable cardiac defibrillator (ICD)

• Lifestyle: diet, alcohol, smoking, exercise